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We herein report a 47-year-old man who presented with progressive paraparesis. Imaging revealed a right upper pulmonary nodule, massive bilateral adrenal metastases, thoracolumbar vertebral osteolysis, and subcutaneous nodules. A biopsy of the right buttock nodule revealed a poorly differentiated metastatic carcinoma with high programmed cell death-ligand 1 expression and extensive chromosomal rearrangements. The patient died 10 days after the initiation of pembrolizumab treatment. Autopsy findings confirmed pulmonary pleomorphic carcinoma with extensive metastases. Quantification of chromosomal rearrangements revealed a jump-up mutation from the normal karyotype, followed by a further incremental increase in the degree of deviation.

The treatment of non-small-cell lung cancer (NSCLC) has progressed from histology-oriented cytotoxic therapy to the era of molecular biology-oriented targeted therapy and immunotherapy. As the first tyrosine kinase inhibitor (TKI) targeting the ROS1 pathway, crizotinib is widely used as a first-line regimen for ROS1 -rearranged NSCLC. However, due to the paucity of solid data from randomized, controlled phase III clinical studies, clinicians often require more systematic, real-world data-based guidance for its optimal clinical use. As one of the leading countries of real-world research on crizotinib, China has contributed significantly to data on standardization of the therapeutic use of crizotinib, including its clinical treatment patterns, the timing and duration of treatment and drug resistance monitoring and management.

Objective: Sublobar resection is considered a standard surgical procedure for early non-small cell lung cancer, although the survival of patients undergoing sublobar resection for clinical T1cN0M0 non-small cell lung cancer remains unclear. This study aimed to compare survival between segmentectomy and wedge resection for clinical T1cN0M0 non-small cell lung cancer., Methods: This retrospective study included patients who had undergone curative surgery for cT1cN0M0 stage IA3 non-small cell lung cancer. The overall and recurrence-free survival rates of 91 patients who underwent segmentectomy or wedge resection were compared., Results: Thirty-nine (42.9%) and 52 patients (57.1%) were included in the segmentectomy and wedge resection groups, respectively. The median length of follow-up was 6.0 years (95% confidence interval 4.2 - - years) (Kaplan-Meier estimate). The 5 year overall survival rates were not significantly different between the segmentectomy and wedge resection groups (67.7% vs 52.0%, P = 0.132). The 5 year recurrence-free survival rate was worse in the wedge resection group than in the segmentectomy group (66.6% vs 46.9%, P = 0.047). In univariable analysis, spread through air spaces (hazard ratio, 5.889; 95% confidence interval, 2.357-14.715; P < 0.001) was an important prognostic factor for recurrence-free survival in the wedge resection group., Conclusions: The overall survival of patients who underwent segmentectomy for clinical T1cN0M0 non-small cell lung cancer was not significantly different from that of patients who underwent wedge resection. However, patients with cT1cN0M0 non-small cell lung cancer who underwent wedge resection tended to have a worse recurrence-free survival prognosis than those who underwent segmentectomy., Competing Interests: Declarations. Conflict of interest: None of the authors have any conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Purpose: Non-small cell lung cancer (NSCLC) is a widespread and serious global malignancy. This study aimed to examine the clinical relevance of serum exosomal SNORD116 and SNORA21 as novel diagnostic biomarkers for NSCLC., Methods: Serum exosomes from 226 healthy controls and 305 NSCLC patients were isolated by ultracentrifugation. Characterization of exosomes was conducted by qNano, transmission electron microscopy (TEM) and Western immunoblotting. RT-PCR revealed snoRNAs that were differentially expressed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance., Results: In NSCLC patients, the levels of serum exosomal SNORD116 and SNORA21 were significantly reduced compared to those in healthy controls (P < 0.0001 for both). ROC curves showed AUC values of 0.738 and 0.761. By combining SNORD116 and SNORA21 with traditional blood biomarkers CYFRA21-1 and carcinoembryonic antigen (CEA), the AUC increased to 0.917. Moreover, these two exosomal snoRNAs distinguished between patients with metastatic NSCLC (n = 132) and those with non-metastatic NSCLC (n = 173) significantly (P < 0.0001 for both). The ROC curves gave AUC values of 0.743 and 0.694, respectively. The combined analysis raised the AUC to 0.751. The diagnostic power of these two exosomal snoRNAs combined with CYFRA21-1 and CEA increased to 0.784., Conclusion: This study demonstrated that serum exosomal SNORD116 and SNORA21 can be used as potential promising non-invasive diagnostic biomarkers for NSCLC., Competing Interests: Declarations. Conflict of interest: No conflict of interest/competing interests to declare. Ethical approval, research involving human participants and animals and informed consent: The studies involving human participants were reviewed and approved by the Affiliated Taian City Central Hospital of Qingdao University (Approval number: 2021-04-02). All patients/participants gave written informed consent in accordance with the Declaration of Helsinki. Consent to participate: All authors have their consent to participate., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Brain metastases (BM) are the most prevalent intracranial malignancies. Approximately 30-40% of cancer patients develop BM at some stage of their illness, presenting with a high incidence and poor prognosis. Our clinical findings indicate a significant disparity in the efficacy between non-enhanced and enhanced lung cancer BM. Therefore, the aim of this study is to conduct a longitudinal MRI evaluation of the therapeutic effect of non-enhanced lung cancer BM, thereby enabling improved efficacy prediction and more personalized treatment plans. We conducted a retrospective analysis of clinical and imaging data from 72 patients with lung cancer BM. Exclusion criteria included participants with a history of primary brain tumors, other malignancies, or neurological symptoms. We performed a longitudinal MRI evaluation of 8 patients with non-enhanced BM who met the eligibility criteria. The response to systemic therapy was locally assessed using the Neuro-Oncology response assessment criteria (RANO 2.0). A total of 8 patients were included in this study, comprising 4 cases of non-enhanced BM and 4 cases featuring both enhanced and non-enhanced BM. The median follow-up time for non-enhanced BM was 19 months, with a disease control rate of 50%. In contrast, the median progression-free follow-up time for enhanced BM was 35.5 months, yielding a disease control rate of 100%. After standardized treatment in accordance with clinical guidelines, patients with enhanced BM exhibited significantly better therapeutic outcomes than those with non-enhanced BM. Cases 1-4 demonstrated non-enhanced or mildly circular-enhanced lung cancer BM, with the sizes of all 4 lesions increasing by over 60% within approximately one year, indicating disease progression. In cases 5-8, each patient presented with two lesions: enhanced (Foci 1) and non-enhanced (Foci 2) BM. Comparative analysis of Foci 1 and Foci 2 revealed significantly weaker treatment responses in non-enhanced lesions (Patients 7-8), with Patient 5 exhibiting disease progression without any response. This study demonstrates that, following standardized treatment protocols aligned with clinical guidelines, the therapeutic effect of non-enhanced lung cancer BM is inferior to that of enhanced BM. Evaluating the enhancement type of lung cancer BM is essential for efficacy prediction and holds important implications for treatment guidance., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Stigma is a pervasive and distressing problem experienced frequently by lung cancer patients, and there is a lack of psychosocial interventions that target the reduction of lung cancer stigma. Mindful self-compassion (MSC) is an empirically supported intervention demonstrated to increase self-compassion and reduce feelings of shame and distress in non-cancer populations. However, there are several anticipated challenges for delivering MSC to lung cancer patients, and modifications may be needed to improve acceptability, appropriateness, and feasibility., Purpose: To gather feedback from lung cancer patients, psycho-oncology researchers, expert MSC teachers, and oncology clinicians to identify themes supporting the adaptation of MSC to reduce lung cancer stigma., Methods: We conducted a two-phase process of stakeholder focus groups with researchers and clinicians (n=12) and semi-structured interviews with lung cancer patients (n=14) with elevated stigma. Transcripts were analyzed using thematic content analysis., Results: Five themes were identified: (i) Patients expressed a desire for an intervention that bolstered self-compassion and addressed stigma; (ii) Intervention instructions were acceptable and understood clearly; (iii) Patients preferred intervention content to directly address lung cancer and stigma yet mentioned that doing so should be done with sensitivity; (iv) Ambivalence about delivering the intervention in person or remotely; (v) Acceptance for an intervention of 8-weeks (or longer) with 90-minute sessions and a group size of ≤ 15., Conclusions: Findings informed the development of an adapted clinical protocol for MSC for lung cancer (MSC-LC), which can be pilot tested to determine implementation outcomes (e.g. acceptability, feasibility, efficacy)., (© Society of Behavioral Medicine 2025. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Lung cancer is the leading cause of cancer-related death. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers and over 60% express wild-type EGFR (WT-EGFR); however, EGFR tyrosine kinase inhibitors (TKIs) have limited effect in most patients with WT-EGFR tumors. In this study, we applied network pharmacology screening and MTT screening of bioactive compounds to obtain one novel grifolic acid that may inhibit NSCLC through the EGFR-ERK1/2 pathway. Through the PPI network and machine learning, we identified two hub genes, EGFR and AKT1, as potential therapeutic targets. Molecular docking confirmed that the grifolic acid could effectively bind to the key target, EGFR. Using the NSCLC cell line NCI-H1781 as an in vitro model, we evaluated the effect of the drugs' combination on viability, apoptosis, and clonogenicity capacity. In vitro studies showed that combined treatment decreased cell viability, increased activation PARP, and caused cell cycle redistribution and significantly greater inhibition of pEGFR and pAKT. This study not only provides new insights into the mechanism of grifolic acid against NSCLC but also important information and new research ideas for the discovery of anti-NSCLC compounds from natural products.

Background: Zorifertinib (AZD3759), an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with high blood-brain barrier penetration capability, demonstrated promising intracranial and systemic antitumor activity in phase 1 and 2 studies in central nervous system (CNS)-metastatic patients., Methods: In this phase 3 EVEREST trial (ClinicalTrials.gov: NCT03653546), patients with EGFR-sensitizing mutations, advanced treatment-naive non-small cell lung cancer (NSCLC), and non-irradiated symptomatic or asymptomatic CNS metastases were randomized (1:1) to zorifertinib or first-generation EGFR-TKI (gefitinib or erlotinib; control). The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival (PFS) per RECIST1.1., Findings: Overall, 439 patients were randomized (zorifertinib n = 220; control n = 219). Most patients had the EGFR L858R mutation (55%) or >3 CNS lesions (54%). Median PFS was significantly longer with zorifertinib versus control (9.6 versus 6.9 months; hazard ratio [HR], 0.719; 95% confidence interval [CI], 0.580-0.893; p = 0.0024). Zorifertinib significantly prolonged intracranial PFS versus control (BICR per modified RECIST1.1: HR, 0.467; 95% CI, 0.352-0.619; investigator per RANO-BM: HR, 0.627; 95% CI, 0.466-0.844). Overall survival (OS) was immature; the estimated median OS was 37.3 months with zorifertinib and 31.8 months with control (HR, 0.833; 95% CI, 0.524-1.283) in patients subsequently treated with third-generation EGFR-TKIs. Safety profiles were consistent with previously reported data for zorifertinib., Conclusions: Zorifertinib significantly improved systemic and intracranial PFS versus first-generation EGFR-TKIs; adverse events were manageable. Sequential use of zorifertinib and third-generation EGFR-TKIs showed the potential to prolong patients' survival. The results favor zorifertinib as a novel, well-validated first-line option for CNS-metastatic patients with EGFR-mutant NSCLC., Funding: This work was funded by Alpha Biopharma (Jiangsu) Co., Ltd., China., Competing Interests: Declaration of interests Q.Z. declares lecture and presentation fees from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi. S.L. declares grants or contracts from AstraZeneca, Hutchison, BMS, Hengrui, BeiGene, Roche, and Hansoh; consulting fees from AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison Medipharma, Simcere, Zai Lab, GenomiCare, Yuhan, prlME Oncology, Menarini, InventisBio, and Roche; lecture and presentation fees from AstraZeneca, Roche, Hansoh, and Hengrui Therapeutics; participation on a data safety monitoring board or advisory board for Roche, Regeneron, AstraZeneca, and Xcovery Holdings; and a leadership or fiduciary role in the Chinese Lung Cancer Associate and CSCO. Z. Wang is an employee of Alpha Biopharma (Jiangsu) and declares no stock ownership in the company. M.-J.A. declares consulting fees from AstraZeneca, Amgen, Merck, Takeda, BMS, ONO, Roche, Daiichi-Sankyo, Janssen, Alpha Pharmaceuticals, Yuhan, Arcus Biosciences, Eutilex, and VORONOI and lecture and presentation fees from AstraZeneca, Amgen, Merck, Takeda, BMS, ONO, Roche, Daiichi-Sankyo, Janssen, and Yuhan. Y.-L.W. declares consulting services for AstraZeneca, Boehringer Ingelheim, Novartis, and Takeda; lecture and presentation fees from AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi; and grants or contracts from AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, and Roche., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dysbiosis of the lung microbiome can contribute to the initiation and progression of lung cancer. Synchronous multiple primary lung cancer (sMPLC) is an increasingly recognized subtype of lung cancer characterized by high morbidity, difficulties in early detection, poor prognosis, and substantial clinical challenges. However, the relationship between sMPLC pathogenesis and changes in the lung microbiome remains unclear., Methods: In this study, 16S rRNA sequencing was performed on clinical samples to analyze lung microbiome composition. Real-time quantitative PCR (qPCR) was used to quantify bacterial abundance in lung tissues. In addition, flow cytometry was conducted to evaluate cell cycle progression and apoptosis in lung tumor cells., Results: Clinical cohort studies demonstrated that sMPLC occurrence is associated with disturbances in the lung microbiome. Notably, Streptococcus intermedius was enriched in the lungs of sMPLC patients compared with non-tumor controls and accumulated preferentially in tumor tissues. S. intermedius shortened the cell cycle and inhibited apoptosis in lung cancer cells. Analyses of oral and gut microbiomes in different patient cohorts revealed a strong correlation between oral microbiome imbalances and lung microbiome composition in sMPLC patients., Conclusions: These findings characterize the lung microbiota in sMPLC and identify S. intermedius as a potentially influential bacterial strain. This study provides significant new insights into the diagnosis and treatment of sMPLC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Deng, Dong, Yang, Krimsky, Tai, Peng, Huang, Xu, Sarkar, Peng and Qian.)

Ferroptosis is of great significance in carcinogenesis as it interconnects with a multiplicity of biological processes. Meanwhile, its function and regulatory role in lung cancer remains ambiguous. In this study, we discovered by WB and IHC that ALYREF has a higher expression in lung adenocarcinoma (LUAD) tissues compared with normal ones. By the direct observation of mitochondria with electron microscopy, we also identified that the knockdown of ALYREF limits the proliferation of LUAD in vitro as well as in vivo and prompts LUAD cells to go through ferroptosis. Mechanistically, our RNA-immunoprecipitation experiment combined with qRT-PCR analysis confirmed that ALYREF could interact with SLC7A11. ALYREF mainly binds to the 3'UTR region of SLC7A11 mRNA, increasing the mRNA stability of SLC7A11 and reducing intracellular Reactive Oxygen Species (ROS) and Methylene diphenyl diamine (MDA) thereby inhibiting ferroptosis and eventually promoting the proliferation and metastasis of LUAD cells. Importantly, our study reveals for the first time that ALYREF can regulate LUAD by inhibiting ferroptosis. Based on the evidences mentioned above, we have good reason to believe that the role of ALYREF as a new oncological factor could be proved and, acting along the ALYREF-SLC7A11-ferroptosis axis, utilized as a promising therapeutic target for LUAD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Solid lung lesions are common in clinical practice, and percutaneous thermal ablation has been shown to be an effective treatment for these lesions. While computed tomography (CT)-guided microwave ablation (MWA) therapy is frequently used for adult solid lesions, it is rarely considered for pediatric cases., Case Presentation: A case of an 8-year-old child with adrenal neuroblastoma and a left upper lung mass. The child successfully underwent lung mass ablation and experienced a long-term progression-free period with good recovery and no recurrence., Conclusions: This case suggests that MWA could be a valuable addition to existing treatment options for solid lesions in children., Competing Interests: Declarations. Ethics approval and consent to participate: The scheme of this report was approved by the Ethics Review Committee of the First Affiliated Hospital of Guangxi Medical University. Written informed consent was obtained from the patient. Consent to publication: Written informed consent was obtained from the participant for publication of identifying information/images in an online open-access publication. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Primary pulmonary meningioma is a rare disease. There have been only a little over 50 cases of primary pulmonary meningioma (PPM) reported in previous literature. The pathogenesis of PPM is still unclear. We report a case of PPM cured by thoracoscopic right middle lobe wedge resection and systematically review previously reported cases in previous literature., Case Report: A 57-year-old male patient was found to have a nodule in the right middle lobe of about 1.8 cm in diameter on a chest-enhanced CT scan performed more than 7 years ago. A re-examination in 2023 found the subpleural nodule in the right middle lobe had grown larger than before. Considering surgical treatment, the patient underwent a thoracoscopic right middle lobe wedge resection after a thorough examination. The final pathological diagnosis was primary pulmonary meningioma. Regular follow-up CT scans showed no recurrence., Conclusion: Primary pulmonary meningioma is a rare tumor that occurs in sites similar to lung cancer. Most cases are solitary, presenting as ground-glass nodules (GGO), and can occur in multiple lobes, involving the mediastinum and pleura with multiple nodules. Clinical and radiological diagnoses are often challenging, especially distinguishing from primary lung cancer. Surgery remains the optimal choice for the diagnosis and treatment of PPM. Most cases are benign with a good prognosis, and wedge resection is usually the preferred surgical approach. A small proportion of malignant cases may require lobectomy and adjuvant radiotherapy and chemotherapy due to tumor invasiveness., Competing Interests: Declarations. Ethics approval and consent to participate: Written informed consent was obtained from the patient to participate in this case report. Consent for publication: We obtained written informed consent for clinical details and clinical images from the patient. A copy of the consent form is available for review by the journal editor. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Diagnosing lung cancer from indeterminate pulmonary nodules (IPLs) remains challenging. In this multi-institutional study involving 2032 participants with IPLs, we integrate the clinical, radiomic with circulating cell-free DNA fragmentomic features in 5-methylcytosine (5mC)-enriched regions to establish a multiomics model (clinic-RadmC) for predicting the malignancy risk of IPLs. The clinic-RadmC yields an area-under-the-curve (AUC) of 0.923 on the external test set, outperforming the single-omics models, and models that only combine clinical features with radiomic, or fragmentomic features in 5mC-enriched regions (p < 0.050 for all). The superiority of the clinic-RadmC maintains well even after adjusting for clinic-radiological variables. Furthermore, the clinic-RadmC-guided strategy could reduce the unnecessary invasive procedures for benign IPLs by 10.9% ~ 35%, and avoid the delayed treatment for lung cancer by 3.1% ~ 38.8%. In summary, our study indicates that the clinic-RadmC provides a more effective and noninvasive tool for optimizing lung cancer diagnoses, thus facilitating the precision interventions., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. JAM2, a member of the Junctional adhesion molecule (JAM) family, plays diverse roles in cell-cell contacts and tumor development. Although JAM2's expression and functions have been reported in various cancers, its clinical and biological significance in LUAD remains unclear., Aims: The aim of this study was to investigate the expression and function of JAM2 in LUAD, and to assess its potential as a prognostic gene and a molecular target for early diagnosis and targeted therapy., Materials: Immunohistochemistry (IHC) was performed on 37 pairs of LUAD tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted among co-expression genes in different JAM2 subgroups. In vitro experiments were also conducted to study the migratory and invasive capabilities of LUAD cells when JAM2 was overexpressed., Results: The study confirmed that JAM2 was downregulated in LUAD, possibly due to methylation. JAM2 emerged as an independent prognostic gene for predicting the outcomes of patients with LUAD. IHC analysis revealed the significance of JAM2 with clinicopathological parameters in LUAD. GO and KEGG analyses provided insights into the biological processes and pathways associated with JAM2. In vitro experiments showed that overexpressing JAM2 significantly suppressed the migratory and invasive capabilities of LUAD cells. Additionally, JAM2 played a crucial role in LUAD inflammatory infiltration, and higher JAM2 expression predicted a better immunotherapy response., Conclusion: JAM2 may serve as a promising molecular target for early diagnosis and targeted therapy of LUAD. Its downregulation in LUAD, potential role as a prognostic gene, and influence on cell migration, invasion, and inflammatory infiltration make it a valuable target for further research and development of therapeutic strategies., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Lung cancer (LC) is a malignant tumor with high morbidity and mortality. Nearly 50% of patients with primary LC have distant metastases at the time of initial diagnosis. LC usually metastasizes from the lungs to the liver, adrenal glands, brain, and bone, but rarely to the gastrointestinal (GI) tract. Most gastrointestinal metastases (GIM) from LC are found on the basis of primary LC. GIM of LC with GI symptoms as the initial symptom is extremely rare. Moreover, the overall survival time of lung cancer patients developing intestinal metastases is from 5 weeks to 1 year, and most patients will die within the first 6 months. This report describes an uncommon case of lung adenocarcinoma that metastasized to the colon with initial symptoms involving the GI tract. After immunotherapy, the condition was stable for more than 2 years, and he is currently in good condition., (© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

While NUSAP1's association with various tumors is established, its predictive value for prognosis and immunotherapy in lung adenocarcinoma (LUAD) remains unconfirmed. We analyzed Nucleolar Spindle-Associated Protein 1 (NUSAP1) gene expression in TCGA and GTEx datasets and validated it in clinicopathological tissues using qRT-PCR and immunohistochemistry. Additionally, we investigated NUSAP1's relationship with patient prognosis across TCGA and five GEO cohorts. The IMvigor210 cohort was utilized to explore NUSAP1's association with immunotherapy efficacy. Furthermore, single-cell RNA-sequencing data was used to examine the correlation between NUSAP1 and immune cell infiltration. Finally, we analyzed the relationship between NUSAP1 and m6A methylation. NUSAP1 expression was significantly elevated in tumor tissues, correlating with poorer prognosis in LUAD patients. It exhibited a significant correlation with immune cell infiltration in the tumor microenvironment, predominantly expressed in Tprolif cells. LUAD patients with heightened NUSAP1 expression may derive greater benefit from anti-PD-L1 treatment. Additionally, NUSAP1 was tightly linked with m6A methylation. Enrichment analysis revealed its association with key biological functions, including lipid metabolism and cell cycle regulation. Our comprehensive analysis underscores NUSAP1's potential as a prognostic and immunotherapeutic biomarker for LUAD, warranting further investigation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Plasma protein has gained prominence in the non-invasive predicting of lung cancer. We utilised Zeolite Zotero NaY-based plasma proteomics to investigate its potential for multiple event predicting, including lung cancer diagnosis (task #1), lymph node metastasis detection (task #2) and tumour‒node‒metastasis (TNM) staging (task #3)., Methods: A total of 4703 plasma proteins were quantified from 241 participants based on a prospective cohort of 2757 participants. An additional 46 participants from external prospective cohort of 735 participants were used for validation. Feature selection was performed using differential expressed protein analysis, area under curve (AUC) evaluation and least absolute shrinkage and selection operator (LASSO) regression. Random forest was used for multitask model construction based on the key proteins. Feature importance was interpreted using Shapley additive explanations (SHAP) algorithm., Results: For task #1, 10 proteins panel showed an AUC of .87 (.77‒.97) in the external validation. After integrating clinical factors, a significant increase diagnostic accuracy was observed with AUC of .91 (.85‒.98). For task #2, nine proteins panel achieved an AUC of .88 (.80‒.96), integration model showed an increase diagnostic accuracy with AUC of .90 (.85‒.97). For task #3, 10 proteins panel showed an AUC of .88 (.74‒.96) for stage I, .92 (.84‒.97) for stage II, .88 (.76‒.96) for stage III and .99 (.98‒.99) for stage IV in the integration model., Conclusions: This study comprehensively profiled the NaY-based plasma proteome biomarker, laying the foundation for a high-performance blood test for predicting multiple events in lung cancer., Key Points: Our study developed an innovative nanomaterial, Zeolite NaY, which addressed the masking effect and improved the depth of the proteome. The performance of NaY-based plasma proteomics as a preclinical diagnostic tool was validated through both internal and external cohort. Furthermore, we explored the different patterns of plasma protein changes during the progression of lung cancer and used the explanations method to elucidate the roles of proteins in the multitask predictive model., (© 2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Tracheal, bronchial, and lung cancers (TBL cancers) pose a significant global health challenge, with rising incidence and mortality rates, particularly in China. Studies from the Global Burden of Disease (GBD), 2021, can guide screening and prevention strategies for TBL cancer. This study aims to provide a comprehensive analysis of the burden of TBL cancers in China compared to global data., Methods: We conducted an analysis of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We also performed Joinpoint regression analysis and Bayesian age-period-cohort (BAPC) modeling to project future trends., Results: From 1990 to 2021, there was a substantial increase in TBL cancer indicators for all sexes in China, with the most significant rise observed in females. The female population showed alarming increases in age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR). While global efforts have managed to stabilize these rates, China's figures remain high, suggesting the impact of persistent risk factors such as smoking and air pollution, coupled with an aging population. Furthermore, we utilized the projection model in China to estimate that these indicators of TBL cancers in females will likely follow continuous and rapid upward trends, while the burden of TBL cancers among males is expected to have a steady trend., Conclusion: Although global efforts have been effective in reducing the burden of TBL cancers over the past three decades, there still remains strong regional and gender heterogeneity. TBL cancers need more screening strategies and medical attention in China and in the female population., (© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Lung cancer is responsible for the highest number of tumor‑related deaths worldwide. A flavonoid extracted from the heartwood of Dalbergia sissoo Roxb., 4‑methoxydalbergione (4‑MD), exhibits potent anticancer activity in multiple malignancies; however, the potential anticancer activity of 4‑MD in lung cancer has not yet been elucidated. In the present study, A549 cells were treated with increasing concentrations of 4‑MD, and cell viability was assessed using a Cell Counting Kit‑8 assay. In addition, colony formation, 5‑ethynyl‑2'‑deoxyuridine, wound healing and Transwell assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Cell morphology was observed using transmission electron microscopy, and ferroptosis was determined using thiobarbituric acid reactive substance, lipid reactive oxygen species (ROS) and iron assays. Moreover, molecular docking was used to verify the potential interaction between 4‑MD and DNA methyltransferase 1 (DNMT1). Tumor‑bearing mice were established and treated with 10 or 30 mg/kg 4‑MD, and tumor volume and weight were recorded. Immunohistochemistry and Prussian blue staining were conducted to examine Ki‑67 expression and iron deposition in tumor tissues, and protein expression was further explored using western blot analysis. The results of the present study revealed that 4‑MD significantly inhibited cell proliferation, migration, invasion and epithelial‑mesenchymal transition in a concentration‑dependent manner. Notably, 4‑MD induced ferroptosis via increased lipid peroxidation, lipid ROS and Fe2+ levels. In addition, it was revealed that 4‑MD can directly bind to DNMT1 to inhibit expression, and inhibit solute carrier family 7 member 11 (SLC7A11; also known as cystine‑glutamate antiporter) and glutathione peroxidase 4 expression. Following DNMT1 overexpression, the observed antitumor activity and ferroptosis‑promoting effects of 4‑MD were partially reversed. Furthermore, 4‑MD significantly inhibited tumor growth in vivo , and reduced tumor volume and weight. In addition, Ki‑67 expression was reduced while iron deposition was increased in the tumor tissues of mice following treatment with 4‑MD. In conclusion, 4‑MD may exhibit anticancer activity through the promotion of DNMT1‑mediated cell ferroptosis. Thus, 4‑MD may have potential as a novel therapeutic agent in the treatment of lung cancer.

Background: This study was designed to explore the action mechanism of stimulator of interferon genes (STING) on the differentiation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment of lung cancer. Methods: Bioinformatics analysis yielded a potential pathway for STING to regulate MDSC differentiation, the interferon regulatory factor 3 (IRF3)/NF-κB axis. The transfection efficiency of STING overexpression plasmid and small interfering RNA against IRF3 (siIRF3) was examined by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection, A9 cells were co-cultured with extracted bone marrow cells (BMCs). MDSC differentiation, protein expression of the IRF3/NF-κB pathway, and changes in nuclear translocation of NF-κB were analyzed by flow cytometry, Western blot, and immunofluorescence staining experiments. A transplanted tumor mouse model was used for in vivo experiments. After cyclic diadenyl monophosphate (CDA; STING agonist) treatment, changes in MDSC differentiation and protein expression of the IRF3/NF-κB axis in transplanted tumors were verified by immunohistochemical staining, qRT-PCR, and Western blot. Results: Coculture of A9 cells and BMCs promoted MDSC differentiation, inhibited activation of IRF3/NF-κB signal in A9 cells, and boosted nuclear translocation of NF-κB. However, after the upregulation of STING, IRF3/NF-κB signal was activated, while MDSC differentiation and nuclear translocation of NF-κB were inhibited. SiIRF3 reversed the effects of STING overexpression. In vivo , CDA dampened MDSC differentiation and promoted protein expression of the IRF3/NF-κB axis. Conclusion: STING signal in lung cancer cells inhibits MDSC differentiation through activation of the IRF3/NF-κB pathway.

Epidermal growth factor receptor (EGFR) is a starring target for the treatment of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat NSCLC patients with EGFR-activating mutations. However, most patients invariably develop resistance to these agents due to the occurrence of novel mutations at the EGFR kinase domain. There is an urgent need to develop more effective therapy strategies to provide more selection for patients with NSCLC. Coccinic acid was reported to exerts potential anti-tumor effects, but its mechanism has not been elucidated and warrants investigation. In this study, coccinic acid was shown to inhibit cell proliferation on cells harboring L858R/T790M mutant EGFR by suppressing p-EGFR and p-STAT3. It was also shown that coccinic acid promoted cell cycle distribution and showed a potent apoptosis-inducing efficacy. Further results in vivo assays demonstrated that coccinic acid reduced tumor growth of NCI-H1975 xenograft in nude mice via the EGFR/STAT3 signaling. Moreover, these effects are involving in the binding of coccinic acid to the EGFR extracellular domain. In conclusion, our finding demonstrated that coccinic acid may be utilized as a potential novel candidate for NSCLC with EGFR L858R/T790M mutation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Accurate detection of driver gene mutations is crucial for treatment planning and predicting prognosis for patients with lung cancer. Conventional genomic testing requires high-quality tissue samples and is time-consuming and resource-consuming, and as a result, is not available for most patients, especially those in low-resource settings. We aimed to develop an annotation-free Deep learning-enabled artificial intelligence method to predict GEne Mutations (DeepGEM) from routinely acquired histological slides., Methods: In this multicentre retrospective study, we collected data for patients with lung cancer who had a biopsy and multigene next-generation sequencing done at 16 hospitals in China (with no restrictions on age, sex, or histology type), to form a large multicentre dataset comprising paired pathological image and multiple gene mutation information. We also included patients from The Cancer Genome Atlas (TCGA) publicly available dataset. Our developed model is an instance-level and bag-level co-supervised multiple instance learning method with label disambiguation design. We trained and initially tested the DeepGEM model on the internal dataset (patients from the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China), and further evaluated it on the external dataset (patients from the remaining 15 centres) and the public TCGA dataset. Additionally, a dataset of patients from the same medical centre as the internal dataset, but without overlap, was used to evaluate the model's generalisation ability to biopsy samples from lymph node metastases. The primary objective was the performance of the DeepGEM model in predicting gene mutations (area under the curve [AUC] and accuracy) in the four prespecified groups (ie, the hold-out internal test set, multicentre external test set, TCGA set, and lymph node metastases set)., Findings: Assessable pathological images and multigene testing information were available for 3697 patients who had biopsy and multigene next-generation sequencing done between Jan 1, 2018, and March 31, 2022, at the 16 centres. We excluded 60 patients with low-quality images. We included 3767 images from 3637 consecutive patients (1978 [54·4%] men, 1514 [41·6%] women, 145 [4·0%] unknown; median age 60 years [IQR 52-67]), with 1716 patients in the internal dataset, 1718 patients in the external dataset, and 203 patients in the lymph node metastases dataset. The DeepGEM model showed robust performance in the internal dataset: for excisional biopsy samples, AUC values for gene mutation prediction ranged from 0·90 (95% CI 0·77-1·00) to 0·97 (0·93-1·00) and accuracy values ranged from 0·91 (0·85-0·98) to 0·97 (0·93-1·00); for aspiration biopsy samples, AUC values ranged from 0·85 (0·80-0·91) to 0·95 (0·86-1·00) and accuracy values ranged from 0·79 (0·74-0·85) to 0·99 (0·98-1·00). In the multicentre external dataset, for excisional biopsy samples, AUC values ranged from 0·80 (95% CI 0·75-0·85) to 0·91 (0·88-1·00) and accuracy values ranged from 0·79 (0·76-0·82) to 0·95 (0·93-0·96); for aspiration biopsy samples, AUC values ranged from 0·76 (0·70-0·83) to 0·87 (0·80-0·94) and accuracy values ranged from 0·76 (0·74-0·79) to 0·97 (0·96-0·98). The model also showed strong performance on the TCGA dataset (473 patients; 535 slides; AUC values ranged from 0·82 [95% CI 0·71-0·93] to 0·96 [0·91-1·00], accuracy values ranged from 0·79 [0·70-0·88] to 0·95 [0·90-1·00]). The DeepGEM model, trained on primary region biopsy samples, could be generalised to biopsy samples from lymph node metastases, with AUC values of 0·91 (95% CI 0·88-0·94) for EGFR and 0·88 (0·82-0·93) for KRAS and accuracy values of 0·85 (0·80-0·88) for EGFR and 0·95 (0·92-0·96) for KRAS and showed potential for prognostic prediction of targeted therapy. The model generated spatial gene mutation maps, indicating gene mutation spatial distribution., Interpretation: We developed an AI-based method that can provide an accurate, timely, and economical prediction of gene mutation and mutation spatial distribution. The method showed substantial potential as an assistive tool for guiding the clinical treatment of patients with lung cancer., Funding: National Natural Science Foundation of China, the Science and Technology Planning Project of Guangzhou, and the National Key Research and Development Program of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests YZha, QR, JWa, KS, JHu, BH, and JY are employees of Tencent. LCh and TH are employees of Burning Rock Biotech. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Lymph node metastasis (LNM) plays a crucial role in the management of lung cancer; however, the ability of chest computed tomography (CT) imaging to detect LNM status is limited., Purpose: This study aimed to develop and validate a vision transformer-based deep transfer learning nomogram for predicting LNM in lung adenocarcinoma patients using preoperative unenhanced chest CT imaging., Methods: This study included 528 patients with lung adenocarcinoma who were randomly divided into training and validation cohorts at a 7:3 ratio. The pretrained vision transformer (ViT) was utilized to extract deep transfer learning (DTL) feature, and logistic regression was employed to construct a ViT-based DTL model. Subsequently, the model was compared with six classical convolutional neural network (CNN) models. Finally, the ViT-based DTL signature was combined with independent clinical predictors to construct a ViT-based deep transfer learning nomogram (DTLN)., Results: The ViT-based DTL model showed good performance, with an area under the curve (AUC) of 0.821 (95% CI, 0.775-0.867) in the training cohort and 0.825 (95% CI, 0.758-0.891) in the validation cohort. The ViT-based DTL model demonstrated comparable performance to classical CNN models in predicting LNM, and the ViT-based DTL signature was then used to construct ViT-based DTLN with independent clinical predictors such as tumor maximum diameter, location, and density. The DTLN achieved the best predictive performance, with AUCs of 0.865 (95% CI, 0.827-0.903) and 0.894 (95% CI, 0845-0942), respectively, surpassing both the clinical factor model and the ViT-based DTL model (p < 0.001)., Conclusion: This study developed a new DTL model based on ViT to predict LNM status in lung adenocarcinoma patients and revealed that the performance of the ViT-based DTL model was comparable to that of classical CNN models, confirming that ViT was viable for deep learning tasks involving medical images. The ViT-based DTLN performed exceptionally well and can assist clinicians and radiologists in making accurate judgments and formulating appropriate treatment plans., (© 2024 American Association of Physicists in Medicine.)

Various studies have reported resistance mechanisms and treatment methods after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatment; however, treatment policies have not yet been established, and few cases have reported transformation to pleomorphic carcinoma (PC) as the resistance mechanism. Herein, we report the case of a 66-year-old woman who was diagnosed with Stage 4A lung adenocarcinoma (cT2bN0M1b) through bronchoscopic biopsy. Genetic profiling revealed an EGFR L858R mutation; therefore, osimertinib was administered as the first-line therapy and achieved a partial response. After 46 months of osimertinib treatment, the metastases remained under control; however, the primary tumor enlarged and was therefore resected. Pathological examination confirmed the diagnosis of PC. Genetic testing of the surgical pathology specimen showed that the EGFR mutation L858R was retained, and the patient was considered drug-resistant owing to the histologic transformation to PC. The patient continued osimertinib therapy and had no recurrence at 9 months postoperatively. Transformation to PC following osimertinib administration is rare, and we report this unique case. This study was approved by the Jichi Medical University Saitama Medical Center Ethics Committee (S24-073), and written informed consent was obtained from the patient., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Despite the advancements in early lung cancer detection attributed to the widespread use of low-dose computed tomography (LDCT), this technology has also led to an increasing number of pulmonary nodules (PNs) of indeterminate significance being identified. Therefore, this study was aimed to develop a model that leverages plasma methylation biomarkers and clinical characteristics to distinguish between malignant and benign PNs., Methods: In a training cohort of 210 patients with PNs, we evaluated plasma circulating tumor DNA (ctDNA) for the presence of three lung cancer-specific methylation markers: SHOX2, SCT, and HOXA7. Subsequently, we constructed a combined model utilizing methylated SHOX2/SCT/HOXA7 (mSHOX2/SCT/HOXA7) ctDNA levels, the largest nodule size measured by LDCT, and age, employing the binary logistic regression algorithm. Furthermore, we compared the diagnostic performances of the combined model with the Mayo Clinic model and the single mSHOX2/SCT/HOXA7 model by analyzing the area under the receiver operating characteristic curve (AUC) for each., Results: The combined model demonstrated an impressive AUC of 0.87 and an accuracy of 0.75 in the training cohort, using pathologic diagnoses as the gold standard. This performance was significantly superior to that of the single mSHOX2/SCT/HOXA7 panel (AUC = 0.81, P < 0.0001) and the Mayo model (AUC = 0.65, P = 0.0005). Further validation in a cohort of 82 patients with PNs confirmed the diagnostic value of the combined model. Additionally, we observed that as the size of the nodule increased, the diagnostic accuracy of the combined model also improved., Conclusions: A combined model incorporating the ctDNA-based methylation status of SHOX2/SCT/HOXA7 genes, the largest nodule size measured by LDCT, and age can serve as a supplementary approach to LDCT for lung cancer. This model enhances the precision in identifying high-risk individuals and optimizes the clinical management strategies for PNs detected by CT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Chemoimmunotherapy is the standard first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC); however, its real-world long-term outcomes associated with patient backgrounds are still unclear. We explored this association using an updated large real-world prospective cohort with a minimum follow-up of 3 years., Methods: This prospective cohort study, conducted across 32 hospitals, enrolled patients with ES-SCLC receiving carboplatin, etoposide, and atezolizumab between September 1, 2019 and September 30, 2020. Updated data with a minimum 3-year follow-up period were analyzed. Patients who met eligibility criteria for pivotal phase 3 clinical trials were considered "trial-eligible.", Results: The median (range) time from the treatment initiation to data cutoff (September 30, 2023) was 42.2 (35.8-48.2) months for the enrolled 207 patients. Most patients (89 %) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients fulfilling the inclusion criteria (132 [64 %]) were categorized as trial-eligible. The 3-year progression-free survival (PFS) probability and overall survival (OS) were 6.1 % and 20.9 %, respectively. The 3-year OS probabilities for trial-eligible and trial-ineligible patients were 26.7 and 9.5 %, respectively. The trial-eligible cohort had a larger percentage of patients achieving a 3-year OS (30/132, 22.7 %) than the trial-ineligible cohort (5/75, 6.7 %) (P = 0.003) CONCLUSIONS: Our study provides the first documentation of the long-term outcomes following chemoimmunotherapy in a large prospective real-world cohort of patients with ES-SCLC. Key eligibility criteria significantly influenced the long-term effectiveness. These findings provide valuable insights into the practical effectiveness of chemoimmunotherapy and clinical decision-making for patients with ES-SCLC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nobuyuki Yamamoto reports financial support was provided by Chugai Pharmaceutical Co Ltd. Daichi Fujimoto reports a relationship with Chugai Pharmaceutical Co Ltd that includes: consulting or advisory and speaking and lecture fees. Motohiro Tamiya reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Akito Hata reports a relationship with Chugai Pharmaceutical Co Ltd that includes: funding grants and speaking and lecture fees. Hirotaka Matsumoto reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Toshihide Yokoyama reports a relationship with Chugai Pharmaceutical Co Ltd that includes: funding grants and speaking and lecture fees. Yoshihiko Taniguchi reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Yuki Sato reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Takashi Kijima reports a relationship with Chugai Pharmaceutical Co Ltd that includes: funding grants and speaking and lecture fees. Hisashi Tanaka reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Naoki Furuya reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Takeshi Masuda reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Yoshihiko Sakata reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Eisaku Miyauchi reports a relationship with Chugai Pharmaceutical Co Ltd that includes: consulting or advisory, funding grants, and speaking and lecture fees. Go Saito reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Satoru Miura reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Teppei Yamaguchi reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Haruko Daga reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Shinya Sakata reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Nobuyuki Yamamoto reports a relationship with Chugai Pharmaceutical Co Ltd that includes: consulting or advisory, funding grants, and speaking and lecture fees. Hiroaki Akamatsu reports a relationship with Chugai Pharmaceutical Co Ltd that includes: funding grants and speaking and lecture fees. Hirotaka Matsumoto reports a relationship with Nippon Kayaku Co Ltd that includes: speaking and lecture fees. Toshihide Yokoyama reports a relationship with Nippon Kayaku Co Ltd that includes: speaking and lecture fees. Yuki Sato reports a relationship with Nippon Kayaku Co Ltd that includes: speaking and lecture fees. Eisaku Miyauchi reports a relationship with Nippon Kayaku Co Ltd that includes: speaking and lecture fees. Satoru Miura reports a relationship with Nippon Kayaku Co Ltd that includes: speaking and lecture fees. Hiroaki Akamatsu reports a relationship with Nippon Kayaku Co Ltd that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Complex interrelationships between the microbiota and cancer have been identified by several studies. However, despite delineating microbial composition in non-small cell lung cancer (NSCLC), key pathogenic microbiota and their underlying mechanisms remain unclear., Methods: We performed 16S rRNA V3-V4 amplicon and transcriptome sequencing on cancerous and adjacent normal tissue samples from 30 patients with NSCLC, from which clinical characteristics and prognosis outcomes were collected. We used 16S rRNA sequencing to dissect microbial composition and perform prognosis correlations, and in conjunction with transcriptome sequencing, we determined potential mechanisms underpinning significant microbiota actions., Results: In comparing different sample types, we identified more pronounced beta diversity disparity between NSCLC, lung squamous cell carcinoma (LUSC) and corresponding paired normal tissues. Concurrently, LUSC and lung adenocarcinoma exhibited distinct microbial composition traits at genus levels. Subsequently, four phyla, five classes, nine orders, 17 families and 36 genera were filtered out and were related to prognosis outcomes. Intriguingly, a protective microbial cluster was identified encompassing nine genera associated with delayed disease recurrence, with functional analyses suggested that these microbiota predominantly exerted metabolism-related functions. Additionally, a harmful microbial cluster (HMC) was identified, including three genera. In this HMC and subsequent prognosis model analyses, harmful intratumoural microbiota were potentially implicated in infection, inflammation and immune regulation. Crucially, we identified a microbial genus, Peptococcus, which was as an independent, detrimental NSCLC prognostic factor and potentially impacted prognosis outcomes via tumour necrosis factor (TNF) signalling., Conclusions: We identified a substantial connection between intratumoural microbiota and NSCLC prognosis outcomes. Protective microbiota primarily exerted metabolic functions, whereas harmful microbiota were mainly implicated in infection, inflammation and immune modulation. Furthermore, Peptococcus may be significant in adverse NSCLC prognoses and serve as a potential biomarker for patient management and cancer screening., Key Points: Four phyla, five classes, nine orders, 17 families and 36 genera have been found associated with NSCLC prognosis. We identified a protective microbial cluster associated with delayed recurrence and a harmful microbial cluster related to shorter survival and earlier recurrence. We identified Peptococcus as an independent, detrimental prognostic factor for NSCLC, potentially impacting prognosis via TNF signalling., (© 2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Brain metastases are a common complication in patients with non-small-cell lung cancer (NSCLC) lacking actionable driver mutations, with limited treatment options and poor prognosis. We aimed to investigate the efficacy and safety of brain radiotherapy combined with camrelizumab and platinum-doublet chemotherapy in patients with newly diagnosed advanced NSCLC and brain metastases., Methods: This multicentre, single-arm, phase 2 trial was done across nine tertiary hospitals in China. Eligible patients were aged 18 years or older, had newly diagnosed brain metastases from NSCLC with no actionable driver mutations (EGFR, ALK, or ROS1), and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were treated with stereotactic radiosurgery or whole-brain radiotherapy combined with camrelizumab (200 mg intravenously once every 3 weeks) and investigator-selected platinum-doublet chemotherapy (pemetrexed 500 mg/m 2 plus platinum [carboplatin, area under curve (AUC) of 5, or cis-platinum 75 mg/m 2 ] for non-squamous NSCLC, and nab-paclitaxel 260 mg/m 2 plus platinum [carboplatin AUC 5, or cis-platinum 75 mg/m 2 ] for squamous NSCLC) for four to six cycles. Patients with controlled disease then received maintenance treatment with camrelizumab alone (200 mg intravenously once every 3 weeks; for squamous NSCLC) or camrelizumab plus pemetrexed (500 mg/m 2 every 3 weeks; for non-squamous NSCLC). The primary endpoint was 6-month progression-free survival rate in the full analysis set, which included all patients who received at least one dose of study treatment regardless of whether they had measurable brain lesions per RECIST 1.1. The trial was registered with ClinicalTrials.gov, NCT04291092, and is ongoing., Findings: Between May 6, 2020, and Jan 30, 2023, 67 patients were assessed for eligibility. Two patients were excluded (brain lesions less than 5 mm) and 65 patients were enrolled and treated. Median age was 66 years (IQR 62-70). 60 (92%) of 65 patients were male and five (8%) were female. All 65 patients were Han Chinese. 50 (77%) of 65 patients had non-squamous NSCLC and 46 (71%) were symptomatic. The 6-month progression-free survival rate was 71·7% (95% CI 58·9-81·1) during the median follow-up of 14·1 months (IQR 9·0-20·3; data cutoff Dec 13, 2023). The most common grade 3-4 treatment-related adverse events were decreased neutrophil count (14 [22%] of 65 patients), decreased white blood cell count (ten [15%]), decreased platelet count (ten [15%]), and decreased lymphocyte count (nine [14%]). Neurological toxic effects of grade 3 occurred in three (5%) of 65 patients. Radiation necrosis occurred in three (5%) of 65 patients; all were grade 1 or 2. There were no treatment-related deaths., Interpretation: Brain radiotherapy combined with camrelizumab and platinum-doublet chemotherapy shows promising efficacy and manageable toxicity and could be a potential treatment option for patients with brain metastases from NSCLC. Randomised controlled trials will be required to confirm these findings., Funding: Beijing Xisike Clinical Oncology Research Foundation and Jiangsu Hengrui Pharmaceuticals., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests FC and XLu are employees of Jiangsu Hengrui Pharmaceuticals. The other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: This study aimed to assess the efficiency of artificial intelligence (AI) in the detection of visceral pleural invasion (VPI) of lung cancer using high-resolution computed tomography (HRCT) images, which is challenging for experts because of its significance in T-classification and lymph node metastasis prediction., Methods: This retrospective analysis was conducted on preoperative HRCT images of 472 patients with stage I non-small cell lung cancer (NSCLC), focusing on lesions adjacent to the pleura to predict VPI. YOLOv4.0 was utilized for tumor localization, and EfficientNetv2 was applied for VPI prediction with HRCT images meticulously annotated for AI model training and validation., Results: Of the 472 lung cancer cases (500 CT images) studied, the AI algorithm successfully identified tumors, with YOLOv4.0 accurately localizing tumors in 98% of the test images. In the EfficientNet v2-M analysis, the receiver operating characteristic curve exhibited an area under the curve of 0.78. It demonstrated powerful diagnostic performance with a sensitivity, specificity, and precision of 76.4% in VPI prediction., Conclusion: AI is a promising tool for improving the diagnostic accuracy of VPI for NSCLC. Furthermore, incorporating AI into the diagnostic workflow is advocated because of its potential to improve the accuracy of preoperative diagnosis and patient outcomes in NSCLC., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Introduction: Hospital admissions often result in functional decline for patients with dementia, yet evidence on the impact of cancer treatments in this population during hospitalization is limited. We aimed to examine the association between dementia and functional decline after cancer treatment in patients with non-small cell lung cancer (NSCLC)., Materials and Methods: A total of 30,213 patients aged 65 years or older hospitalized for NSCLC treatment, from a dataset of 366 acute care hospitals in Japan, were eligible for this study. The primary outcome was activities of daily living (ADL) at discharge, assessed using the Barthel Index, with a total score ranging from 0 to 100, and the secondary outcome was the length of hospital stay. We conducted causal mediation analysis by cancer treatment within a counterfactual framework using the g-formula approach with direct counterfactual imputation. Bias-corrected and adjusted bootstrapped 95 % confidence intervals (CIs) were calculated based on 100 bootstrap samples. Dementia status served as the exposure, ADL scores at admission as the mediator, and ADL scores at discharge as the outcome. Covariates measured at admission were used to adjust for dementia status. Subgroup analyses were performed by treatment group including surgery., Results: Compared with patients with NSCLC who did not have dementia, those with dementia exhibited lower ADLs at discharge across most cancer treatments, regardless of ADL scores at admission. Patients with dementia who underwent chemotherapy had prolonged hospital stays of 2.90 days longer (95 % CI, 1.27 to 4.52) and lower ADL scores at discharge than their counterparts without dementia (-9.77 [95 % CI, -12.55 to -7.00]). Similarly, patients with dementia who received radiotherapy experienced lower ADL scores at discharge compared with those without dementia (-15.06 [95 % CI, -19.59 to -10.54]), with no difference in the length of hospital stay (-0.54 [95 % CI, -2.84 to 1.75] days). Similar findings were observed from the total effects after adjusting for potential confounders., Discussion: Patients with comorbid cancer and dementia consistently displayed lower ADL scores at discharge following various cancer treatments. Understanding the effects of dementia on functional decline may aid in making optimal treatment choices for inpatient care for patients with NSCLC., Competing Interests: Declaration of Competing Interest The authors do not report any conflict of interest related to this manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Chronic stress can significantly promote breast cancer progression. When exposed to chronic stress, exosomes released from neural and neuroendocrine cells in the central nervous system are enhanced and modified. However, whether tumor-derived exosomes (TDEs) are influenced by chronic stress and participate in chronic stress-mediated distant metastasis remains unclear. Here, it is shown that chronic stress remarkably facilitates the secretion of TDEs and modifies the contents of exosomes by activating the adrenergic β receptor in 4T1 tumor-bearing mice. Exosomes injection and blockade experiments indicate that exosomes play a crucial role in chronic stress-mediated lung metastasis of breast cancer. Chronic stress-induced TDEs are internalized by pulmonary neutrophils and strengthen neutrophil recruitment via the CXCL2 autocrine. In addition, the level of SP1 in TDEs increases, which favors the secretion of IL-1β by neutrophils through the activation of the TLR4-NFκβ pathway, ultimately aggravating lung metastasis of breast cancer. Collectively, this study provides a novel mechanism by which neutrophils within a pre-metastatic niche acquire their inflamed phenotype and establishes an important link among neuroendocrine changes, exosomes, immunity, and metastasis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The proliferation, metastasis, and drug resistance of cancer cells pose significant challenges to the treatment of lung squamous cell carcinoma (LUSC). However, there is a lack of optimal predictive models that can accurately forecast patient prognosis and guide the selection of targeted therapies. The extensive multi-omic data obtained from multi-level molecular biology provides a unique perspective for understanding the underlying biological characteristics of cancer, offering potential prognostic indicators and drug sensitivity biomarkers for LUSC patients. We integrated diverse datasets encompassing gene expression, DNA methylation, genomic mutations, and clinical data from LUSC patients to achieve consensus clustering using a suite of 10 multi-omics integration algorithms. Subsequently, we employed 10 commonly used machine learning algorithms, combining them into 101 unique configurations to design an optimal performing model. We then explored the characteristics of high- and low-risk LUSC patient groups in terms of the tumor microenvironment and response to immunotherapy, ultimately validating the functional roles of the model genes through in vitro experiments. Through the application of 10 clustering algorithms, we identified two prognostically relevant subtypes, with CS1 exhibiting a more favorable prognosis. We then constructed a subtype-specific machine learning model, LUSC multi-omics signature (LMS) based on seven key hub genes. Compared to previously published LUSC biomarkers, our LMS score demonstrated superior predictive performance. Patients with lower LMS scores had higher overall survival rates and better responses to immunotherapy. Notably, the high LMS group was more inclined toward "cold" tumors, characterized by immune suppression and exclusion, but drugs like dasatinib may represent promising therapeutic options for these patients. Notably, we also validated the model gene SERPINB13 through cell experiments, confirming its role as a potential oncogene influencing the progression of LUSC and as a promising therapeutic target. Our research provides new insights into refining the molecular classification of LUSC and further optimizing immunotherapy strategies., (© 2024 International Union of Biochemistry and Molecular Biology.)

Importance: Physical biomarkers for stratifying patients with lung cancer into subtypes suggestive of outcomes are underexplored., Objective: To investigate the clinical utility of respiratory sarcopenia for optimizing postoperative risk stratification in patients with non-small cell lung cancer (NSCLC)., Design, Setting, and Participants: This retrospective cohort study reviewed consecutive patients undergoing lobectomy and mediastinal lymph node dissection for NSCLC at 2 institutions in Tokyo, Japan, between 2009 and 2018. Eligible patients underwent electronic computed tomography image analysis. Follow-up began at the date of surgery and continued until death, the last contact, or March 2022. Data analysis was performed from April 2022 to March 2023., Main Outcomes and Measures: Respiratory sarcopenia was identified by poor respiratory strength (peak expiratory flow rate) and was confirmed by a low pectoralis muscle index (PMI; pectoralis muscle area/body mass index). Patients with poor peak expiratory flow rate but normal PMI received a diagnosis of pre-respiratory sarcopenia. Short-term and long-term postoperative outcomes were compared among patients with a normal status, pre-respiratory sarcopenia, and respiratory sarcopenia. Group differences were analyzed using the Kruskal-Wallis test and Pearson χ2 test for continuous and categorical data, respectively. Survival differences were compared using the log-rank test. Univariable and multivariable analyses were conducted using the Cox proportional hazards model., Results: Of a total of 1016 patients, 806 (497 men [61.7%]; median [IQR] age, 69 [64-76] years) were eligible for electronic computed tomography image analysis. The median (IQR) duration of follow-up for survival was 5.2 (3.6-6.4) years. Respiratory strength was more closely correlated with PMI than pectoralis muscle radiodensity (Pearson r2, 0.58 vs 0.29). Respiratory strength and PMI declined with aging simultaneously (both P for trend < .001). Pre-respiratory sarcopenia was present in 177 patients (22.0%), and respiratory sarcopenia was present in 130 patients (16.1%). The risk of postoperative complications escalated from 82 patients (16.4%) with normal status to 39 patients (22.0%) with pre-respiratory sarcopenia to 39 patients (30.0%) with respiratory sarcopenia (P for trend < .001), as did the risk of delayed recovery after surgery (P for trend < .001). Compared with patients with normal status or pre-respiratory sarcopenia, patients with respiratory sarcopenia exhibited worse 5-year overall survival (438 patients [87.2%] vs 133 patients [72.9%] vs 85 patients [62.5%]; P for trend < .001). Multivariable analysis identified respiratory sarcopenia as a factor independently associated with increased risk of mortality (hazard ratio, 1.83; 95% CI, 1.15-2.89; P = .01) after adjustment for sex, age, smoking status, performance status, chronic heart disease, forced expiratory volume in 1 second, diffusing capacity for carbon monoxide, C-reactive protein, albumin, carcinoembryonic antigen, histology, and pathologic stage., Conclusions and Relevance: This study identified individuals at higher risk of poor outcomes by screening and staging respiratory sarcopenia. The early diagnosis of respiratory sarcopenia could optimize management strategies and facilitate longitudinal care in patients with NSCLC.

Abstract: We present the 18 F-FDG PET/CT findings of a 64-year-old man with isolated renal metastasis. He had a history of radical surgery for squamous cell lung cancer 14 months ago, followed by chemotherapy and immunotherapy. The renal metastasis presented as a small focus of increased FDG uptake in the restaging 18 F-FDG PET/CT scan, which was regarded as renal cortical tracer retention. The renal metastasis was more prominent on the second PET/CT performed 5 months later. The patient subsequently underwent radical nephrectomy, and histopathological examination confirmed the diagnosis of renal squamous cell carcinoma metastasis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Cancer involves tumor cells and tumor-specific immunity. The ability to accurately quantify tumor-specific immunity is limited. Most immunotherapies function by activating new effector tumor antigen-specific T cells (ETASTs) or reactivating the pre-existing ETASTs repertoire. Therefore, the amount of ETASTs can be used to characterize immunotherapy efficacy. Tumor antigens are highly heterogeneous and detecting most ETASTs is challenging. Therefore, nanoparticles loading whole-cell tumor antigens are used to activate and detect pan-clones ETASTs in the blood. The differences between ETASTs and other T cells are transformed into activated and non-activated states. By measuring markers of the activated status and cytotoxic function of ETASTs, it can distinguish ETASTs from other T cells. ETASTs in patients with lung cancer are higher than those in healthy individuals and those with benign pulmonary nodules. Therapeutic efficacy positively correlated with the number of ETASTs in the blood. ETATS levels increase only in the blood of patients who respond to immunotherapy. Single-cell sequencing studies validated these findings. This study provides a highly accurate, specific, non-invasive, and efficient biomarker for predicting immunotherapy efficacy in lung and other cancers. This method can also be applied to evaluate the efficacy of other treatments, such as radiotherapy, oncolytic viruses, and nanomedicine-based therapies., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Immune-related dissociated response (DR) has been recently recognized and have become a subject of ongoing interest. The purpose of the present study was to evaluate the frequency, treatment outcome, and predictors of DR in cancer patients with immune checkpoint inhibitors. We retrospectively collected clinicopathological data from a cohort of patients with cancer who received PD-1/PD-L1 inhibitor-based monotherapy or combination therapy at a single institution (developing cohort). An independent cohort of advanced non-small cell lung cancer (NSCLC) patients treated with immunotherapy at two institutions was used as the validating cohort. Progression-free survival (PFS) and overall survival (OS) were used as outcome measures. The pantumor cohort included 177 patients. DR were observed in 12 (6.8%) patients. The median PFS and OS were significantly longer in patients with atypical response versus nonresponse but shorter versus true response. Patients with DR had a longer median PFS and OS than those with true progressive disease (PD). Local treatment seemed to have a positive influence on DR patient outcomes, with a median OS of 32.3 months versus 21.9 months for no local treatment. No clinical characteristics remained significant predictors for DR. In the NSCLC cohort, DR was observed in 10 (12.5%) patients. Inferior PFS and OS were validated in patients with real PD when compared with patients with DR. Patients who experience DR exhibit a relatively favorable prognosis. Some patients with DR may benefit from the continuation of ICI administration and local treatment to the growing lesions and achieve a longer survival., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the independent research ethics committee of The First Affiliated Hospital of Shandong First Medical University (NO: YXLL-KY-2022–059) and conformed to the principles of the Declaration of Helsinki., (© 2024. The Author(s).)

Renal abscesses require prompt diagnosis and appropriate intervention, as they can be life-threatening. However, diagnosis based solely on clinical findings is often challenging. We present the case of a 69-year-old woman with left renal masses on follow-up computed tomography (CT) after surgery for pT2aN0M0 lung carcinosarcoma. The masses were localized only in the left kidney without suspected metastatic lesions at other sites. The patient was referred to our department for further evaluation and treatment under a diagnosis of suspected metastatic lung carcinosarcoma of the left kidney. On enhanced CT, the left renal masses, the largest of which had a diameter of 40×36 mm had thick irregular walls gradually enhanced by the contrast media and an internal low-attenuation area. The masses showed heterogeneous signal intensity with a pseudocapsule on T2-weighted magnetic resonance imaging. Clinical symptoms such as fever or costovertebral angle tenderness were absent, and blood and urine tests were not sufficiently inflammatory to suggest a renal abscess. Histopathological findings on CT-guided renal biopsy revealed only inflammatory tissue and no tumor cells. However, because lung carcinosarcoma metastatic nodules could not be ruled out, laparoscopic left nephrectomy was performed for a definitive diagnosis and curative intent. The pathological diagnosis was renal abscess without malignant lesions. Here, we present a case of renal abscess mimicking metastatic lesions in a patient with lung carcinosarcoma. Accurately differentiating renal abscesses from metastatic renal tumors before treatment is often difficult. Renal abscess diagnosis should be considered through a comprehensive evaluation of the clinical findings of individual cases.

Anoikis, a form of programmed cell death induced by loss of cell contact, is closely associated with tumor invasion and metastasis, making it highly significant in lung cancer research. We examined the expression patterns and prognostic relevance of Anoikis-related genes (ARGs) in lung adenocarcinoma (LUAD) using the TCGA-LUAD database. This study identified molecular subtypes associated with Anoikis in LUAD and conducted functional enrichment analyses. We constructed an ARG risk score using univariate least absolute shrinkage and selection operator (LASSO) Cox regression, validated externally with GEO datasets and clinical samples. The clinical applicability of the prognostic model was evaluated using nomograms, calibration curves, decision curve analysis (DCA), and time-dependent AUC assessments. We identified four prognostically significant genes (PLK1, SLC2A1, CDKN3, PHLDA2) and two ARG-related molecular subtypes. ARGs were generally upregulated in LUAD and correlated with multiple pathways including the cell cycle and DNA replication. The prognostic model indicated that the low-risk group had better outcomes and significant correlations with clinicopathological features, tumor microenvironment, immune therapy responses, drug sensitivity, and pan-RNA epigenetic modification-related genes. Patients with low-risk LUAD were potential beneficiaries of immune checkpoint inhibitor (ICI) therapy. Prognostic ARGs' distribution and expression across various immune cell types were further analyzed using single-cell RNA sequencing. The pivotal role of CDKN3 in LUAD was confirmed through qRT-PCR and gene knockout experiments, demonstrating that CDKN3 knockdown inhibits tumor cell proliferation, migration, and invasion. Additionally, we constructed a ceRNA network involving CDKN3/hsa-miR-26a-5p/SNHG6, LINC00665, DUXAP8, and SLC2A1/hsa-miR-218-5p/RNASEH1-AS1, providing new insights for personalized and immune therapy decisions in LUAD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.8 months) in the toripalimab group than that in the control group (17.0 months). (HR = 0.69, 95%CI: 0.57-0.93, nominal P = 0.01). This survival benefit was particularly notable in the non-squamous subgroup. As the first phase 3 study to perform both baseline tissue whole-exome sequencing (WES) and peripheral blood ctDNA testing, we investigated efficacy predictive biomarkers based on both tissue and ctDNA, Genomic sequencing of ctDNA showed high concordance with tumor tissue independently confirmed that individuals exhibiting a high tumor mutational burden, as well as mutations in the FA-PI3K-Akt and IL-7 signaling pathways benefited more from the toripalimab treatment. Furthermore, a ctDNA response observed on cycle 3 day 1, was associated with improved clinical outcomes for patients treated with the combination therapy. In conclusion, Toripalimab plus chemotherapy yields significant improvements in OS as a first-line treatment. The study highlights the utility of ctDNA as a proxy for tumor tissue, providing novel prospects for predicting efficacy of immuno-chemotherapy through continuous ctDNA monitoring., Competing Interests: Competing interests: Jianjun Yu and Sheng Yao are the employee of Shanghai Junshi Biosciences and TopAlliance Biosciences; Xianmin Luo is the employee of Shanghai Junshi Biosciences, Shangli Cai and Yiran Cai are the employee of Burning Rock Biotech. All the other authors declare no conflict of interests., (© 2024. The Author(s).)

O-GlcNAcylation catalyzed by O-GlcNAc transferase (OGT) plays an important role in the regulation of tumor glycolysis. However, the mechanism underlying OGT regulation remains largely unknown. Here, we showed that coactivator associated arginine methyltransferase 1 (CARM1) sensed changes of extracellular glucose levels in non-small cell lung cancer (NSCLC) cells. Increased glucose upregulated CARM1 and OGT. CARM1 methylated OGT at arginine 348, promoting its stability through binding of the deubiquitinase USP9X. The arginine methylation of OGT increased global O-GlcNAcylation levels, thereby promoting glycolysis in NSCLC cells. OGT arginine methylation also upregulated c-Myc expression and promoted the proliferation of NSCLC cells in vitro and in vivo. Consistently, OGT expression was positively correlated with CARM1 in human NSCLC samples. The present findings shed light on the mechanism underlying the stabilization of OGT by arginine methylation in response to changes of glucose concentration. The study also clarified the role of the CARM1-USP9X-OGT axis in glycolysis in NSCLC, providing a potential new target or therapeutic strategy in NSCLC., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were conducted in accordance with relevant guidelines and regulations, including the principles outlined in the Declaration of Helsinki. Informed consent was obtained from all patients. Ethics approval for human subjects was provided by China-Japan Union Hospital of Jilin University(Authorization number: 2023122705). Ethics approval for animal work was provided by the Animal Care Committee of Northeast Normal University (Authorization number: 202402013)., (© 2024. The Author(s).)

Background: Pulmonary nodule ablation is an effective method for treating pulmonary nodules. This study is based on the traditional CT-guided percutaneous microwave ablation (MWA) of pulmonary nodules. By comparing laser guidance technology with freehand method, this study aims to explore the safety and efficacy and patients' pain scores of these two approaches., Methods: This study retrospectively analyzed 126 patients who underwent CT-guided percutaneous lung ablation at the First Affiliated Hospital of Soochow University from April 2020 to April 2024. Based on the guidance method, we divided those patients into the laser guidance group and the freehand group. The primary outcome such as operation time, the number of ablation needle adjustments, postoperative pain scores, postoperative hospital stay, and postoperative complications were analyzed., Results: The laser guidance group had a significantly shorter mean operation time compared to the freehand group (39.3 ± 13.65 min vs. 43.82 ± 19.12 min, p < 0.01), and in the laser guidance group, fewer ablation needle adjustments were required than in the freehand group (3.3 ± 1.34 time vs. 4.37 ± 1.39 times, p < 0.001). As compared to the freehand group, the laser guidance group had fewer cases of mild pneumothorax (13.16% vs. 38.33%, p < 0.05). The postoperative pain score at 1 h and 1 day of the two groups showed no statistical difference., Conclusion: Both methods are safe and effective. The laser guidance technology significantly reduces the number of puncture adjustments and the operation time compared to the freehand method. Laser guidance technology effectively reduces the incidence of mild pneumothorax., Competing Interests: Declarations. Ethical approval and consent to participate: Ethical approval from the ethics committee of the First Affiliated Hospital of Soochow University was granted for this study. Informed consent was obtained from all patients participating in this study and all methods were performed according to the relevant guidelines and regulations Registration number: no. 2023510. Consent to publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To develop a multimodal predictive model, Radiomics Integrated TLSs System (RAITS), based on preoperative CT radiomic features for the identification of TLSs in stage I lung adenocarcinoma patients and to evaluate its potential in prognosis stratification and guiding personalized treatment., Methods: The most recent preoperative chest CT thin-slice scans and postoperative hematoxylin and eosin-stained pathology sections of patients diagnosed with stage I LUAD were retrospectively collected. Tumor segmentation was achieved using an automatic virtual adversarial training segmentation algorithm based on a three-dimensional U-shape convolutional neural network (3D U-Net). Radiomic features were extracted from the tumor and peritumoral areas, with extensions of 2 mm, 4 mm, 6 mm, and 8 mm, respectively, and deep learning image features were extracted through a convolutional neural network. Subsequently, the RAITS was constructed. The performance of RAITS was then evaluated in both the train and validation cohorts., Results: RAITS demonstrated superior AUC, sensitivity, and specificity in both the training and external validation cohorts, outperforming traditional unimodal models. In the validation cohort, RAITS achieved an AUC of 0.78 (95% CI, 0.69-0.88) and showed higher net benefits across most threshold ranges. RAITS exhibited strong discriminative ability in risk stratification, with p < 0.01 in the training cohort and p = 0.02 in the validation cohort, consistent with the actual predictive performance of TLSs, where TLS-positive patients had significantly higher recurrence-free survival (RFS) compared to TLS-negative patients (p = 0.04 in the training cohort, p = 0.02 in the validation cohort)., Conclusion: As a multimodal predictive model based on preoperative CT radiomic features, RAITS demonstrated excellent performance in identifying TLSs in stage I LUAD and holds potential value in clinical decision-making., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the ethical review committee of Tianjin Chest Hospital. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Lung adenocarcinoma (LUAD) is the common form of lung cancer and is prone to distant metastasis. IGF2BP2, an m6A modification regulator, is upregulated in lung cancer tissue, but its specific role within the LUAD tumor microenvironment (TME) is unknown. We explored the role of IGF2BP2 in the progression of LUAD. IGF2BP2 expression in LUAD patient specimens and controls was evaluated through bioinformatics, Western blot, and immunohistochemistry. LUAD subcutaneous and orthotopic xenograft tumor models were established, alongside a co-culture system of tumor-associated neutrophils (TANs) and A549 cells. Functional assays assessed IGF2BP2's role under treatment with JX5, an IGF2BP2 inhibitor. Mechanistic assays explored the interaction between IGF2BP2 and LOX1 in 293T cells. IGF2BP2 was significantly upregulated in LUAD tissues, with higher expression levels predicting worse prognosis for patients (p < 0.001). In subcutaneous and orthotopic xenograft models, treatment with JX5, an IGF2BP2 inhibitor, reduced tumor size, volume, and weight (p < 0.001). JX5 also significantly reduced the concentrations of pro-inflammatory cytokines in peripheral blood (p < 0.01 and p < 0.001). Flow cytometry analysis indicated JX5 reduced CD11b+Ly6G+/CD45+ cells (TANs) in the TME (p < 0.001). Mechanistically, JX5 downregulated LOX1 expression in vivo, and co-culture experiments further demonstrated that IGF2BP2 promotes LUAD progression through LOX1-mediated regulation of TAN activity (p < 0.01 and p < 0.001). Overexpression of LOX1 reversed the inhibitory effects of JX5 on TAN infiltration, tumor cell viability, and apoptosis (p < 0.01 and p < 0.001). Additionally, RNA immunoprecipitation revealed that IGF2BP2 binds to LOX1 mRNA at its m6A modification site, stabilizing LOX1 and enhancing its function in the TME. Knockdown of IGF2BP2 accelerated LOX1 mRNA degradation, confirming its role in maintaining LOX1 stability (p < 0.01 and p < 0.001). IGF2BP2 recognizes and stabilizes LOX1 through m6A modification, contributing to TAN-mediated LUAD progression. Overall, these findings offer new insights into LUAD progression and demonstrate that IGF2BP2 is a key regulator that promotes tumor advancement, highlighting the IGF2BP2-LOX1 axis as a potential therapeutic target for LUAD., Competing Interests: Declarations. Ethical approval: Animal study and human ethical approval were given by the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University (KY-2024-173-01, human study) and Laboratory Animal Center Ethics Committee of Soochow University (202306A0917, animal study). Competing interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for patients with non-small cell lung cancer (NSCLC). In spite of durable responses in some patients, many patients develop early disease progression during the ICI treatment. Thus, early identification of patients with no durable benefit would facilitate the clinical decision for these patients. In this prospective, multicenter study, 101 non-EGFR/ALK patients who received ICI treatment were enrolled after screening 328 stage III-IV NSCLC patients. At the date of cutoff, 83 patients were eligible for ICI efficacy evaluation, with 56 patients having progress-free survival (PFS) over 6 months, which was defined as durable clinical benefit (DCB). A multimodal model was established by integrating normalized bTMB, early dynamic of ctDNA and the first RECIST response. This model could robustly predict DCB with area under the curve (AUC) of 0.878, sensitivity of 79.2% at 86.4% specificity (accuracy = 80.0%). This model was further validated in the independent cohort of the DIREct-On study with AUC of 0.887, sensitivity of 94.7% at 85.3% specificity (accuracy = 90.3%). Patients with higher predict scores had substantially longer PFS than those with lower scores (training cohort: median PFS 13.6 vs 4.2 months, P < 0.001, HR = 0.24; validation cohort: median PFS 11.0 vs 2.2 months, P < 0.001, HR = 0.17). Taken together, these results demonstrate that integrating early changes of ctDNA, normalized bTMB, and the first RECIST response can provide accurate, noninvasive, and early prediction of durable benefits for NSCLC patients treated with ICIs. Further prospective studies are warranted to validate these findings and guide clinical decision-making for optimal immunotherapy in NSCLC patients., Competing Interests: Competing interests: Yuanyuan Xiong, Huan Yin, and Rongrong Chen were the employees of Geneplus-Beijing, other authors declare no potential conflict of interests., (© 2024. The Author(s).)

Purpose: Angiogenesis inhibitors are known to modify tumor immunity. Combination of angiogenesis inhibitors with immune checkpoint inhibitors has shown efficacy against many types of cancers, including non-small cell lung cancer (NSCLC). We investigated the feasibility of neoadjuvant therapy with pembrolizumab and ramucirumab, a VEGFR-2 antagonist for patients with PD-L1-positive NSCLC, and its influence on the tumor microenvironment., Patients and Methods: Patients with pathologically proven, PD-L1-positive, clinical stage IB to IIIA NSCLC were eligible. Patients received two cycles of pembrolizumab (200 mg/body) and ramucirumab (10 mg/kg) every 3 weeks. Surgery was scheduled 4 to 8 weeks after the last dose. The primary endpoint was the major pathologic response rate by a blinded independent pathologic review. The sample size was 24 patients. Exploratory endpoints were evaluated to elucidate the effects of neoadjuvant therapy on the tumor microenvironment., Results: The 24 eligible patients were enrolled between July 2019 and April 2022. The major pathologic response rate was 50.0% (90% confidence interval, 31.9%-68.1%). Six patients showed pathologic complete response. Grade 3 adverse events (AE) occurred in nine patients (37.5%), including three immune-related AEs (acute tubulointerstitial nephritis in two cases and polymyalgia rheumatica in one case). There were no grade 4 or 5 AEs. The transcriptome and multiplex IHC results suggested that tumors with greater CD8+ T-cell infiltration and higher expression of effector molecules at the baseline could show better sensitivity to treatment., Conclusions: This new neoadjuvant combination of pembrolizumab plus ramucirumab was feasible, and anti-VEGF agents may enhance the effects of immune checkpoint inhibitors., (©2024 American Association for Cancer Research.)

The growth differentiation factor 15 (GDF15) may serve as a biomarker of metformin, which mediates the bodyweight lowering effect of metformin. However, whether GDF15 also serves as a molecular target of metformin to inhibit carcinogenesis remains largely unknown. This study examined the role and molecular mechanisms of GDF15 in the anticancer effects of metformin in non-small cell lung cancer (NSCLC) cells, which has never been reported before. We found that metformin significantly inhibited the migration of NSCLC A549 and NCI-H460 cells and reduced the expression of epithelial-to-mesenchymal transition (EMT)-related molecules, including neuro-cadherin (N-cadherin), matrix metalloproteinase 2 (MMP2), and the zinc finger transcription factor Snail, but increased epithelial cadherin (E-cadherin) expression. Furthermore, metformin increased GDF15 and its upstream transcription factors activated transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP) expressions and increased AMP-activated protein kinase (AMPK) phosphorylation in NSCLC cells. GDF15 siRNA partially reverses the inhibitory effect of metformin on NSCLC cell migration. Moreover, metformin-induced increases in GDF15, CHOP, and ATF4 expression and the inhibition of migration were partially reversed by treatment with Compound C, a specific AMPK inhibitor. Meanwhile, metformin significantly inhibited NCI-H460 xenograft tumor growth in nude mice, increased GDF15 expression, and regulated EMT- and migration-related protein expression in xenograft tumors. In conclusion, our results provide novel insights into revealing that GDF15 can serve as a potential molecular target of metformin owing to its anti-cancer effect in NSCLC, which is mediated by AMPK activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The interaction of tumor cells and their microenvironment is thought to be a key factor in tumor development. We present spatial RNA profiles obtained from 30 lung adenocarcinoma patients at the non-invasive and later invasive stages. We use spatial transcriptome sequencing data in conjunction with in situ RNA profiling to conduct higher resolution analyses. The detailed examination of each case, as well as the subsequent computational analyses based on the observed diverse profiles, reveals that significant changes in the phenotypic appearances of tumor cells are frequently associated with changes in immune cell features. The phenomenon coincides with the induction of a series of cellular expression programs that enable tumor cells to transform and break through the immune cell barrier, allowing them to progress further. The study shows how lung tumors develop through interaction in their microenvironments., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: This study aims to explore how pre-existing conditions such as blood types, family history of cancer and comorbid diseases correlate with the genetic and programmed death-ligand 1 (PD-L1) expression that contributes to the heterogeneous biological behaviours of non-small cell lung cancer (NSCLC)., Materials and Methods: A cohort of 5507 NSCLC patients who underwent surgical resection between January 2014 and July 2018 was studied. Targeted next-generation sequencing was used to detect mutations in nine pivotal cancer-related genes, and immunohistochemical staining was applied to assess PD-L1 expression. Logistic regression analysis was employed to identify significant correlations., Results: All patients underwent NGS, with 1839 were also evaluated for PD-L1 expression. Several significant findings were found: ROS1 mutations were closely associated with a family history of lung cancer (OR 7.499, 95% CI 1.094 to 30.940, p=0.013). Epidermal growth factor receptor (EGFR) L858R mutations were common among patients with a family history of non-lung cancers and those with hypertension (OR 2.089, 95% CI 1.029 to 4.135, p=0.037 and OR 1.252, 95% CI 1.001 to 1.562, p=0.048, respectively). Pre-existing conditions such as diabetes and hepatitis B surface antigen positivity (OR 1.468, 95% CI 1.042 to 2.047, p=0.026 and OR 1.373, 95% CI 1.012 to 1.847, p=0.038, respectively) were correlated with EGFR exon 19 deletions. RhD negativity showed potential ties to BRAF mutations (OR 0.010, 95% CI 0.001 to 0.252, p=0.001). A history of tuberculosis linked to increased PD-L1 expression in immune cells (OR 3.597, 95% CI 1.295 to 14.957, p=0.034)., Conclusion: This large-scale, cross-sectional study reveals a complex interplay between genetic mutations, immunological features and pre-existing conditions in NSCLC patients, offering insights that could inform personalised treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This retrospective study aimed to determine the need for lymph node resection during surgical treatment in patients with stage IA non-small-cell lung cancer (NSCLC)., Materials and Methods: A total of 1428 patients diagnosed with cT1N0M0 1 A stage NSCLC who underwent surgery were divided into two groups: lymphadenectomy (n = 1324) and nonlymphadenectomy (n = 104). The effects of lymph node resection on overall survival (OS) and recurrence-free survival (RFS) and on clinicopathological factors that affected the prognosis of the patients were investigated., Results: The group that underwent lymph node resection had a better 5-year OS (89.2% vs 81.1%) and 3-year RFS (87.6% vs 79.2%) than the one that did not. Multivariate Cox regression analysis revealed that the risk of OS in the nonlymphadenectomy group increased by 72% compared to that in the lymphadenectomy group [hazard ratio (HR), 1.72; 95% confidence interval (CI), 1.08-2.74; P < 0.05]. The risk of RFS in the group without lymphadenectomy increased by 45% compared to that in the group with lymphadenectomy (HR, 1.45; 95% CI, 0.98-2.14;P = 0.06). Significant reductions in the OS (HR, 5.90; 95% CI, 1.80-20.00; P < 0.005) and RFS (HR, 4.00; 95% CI, 1.50-11.00;P < 0.005) can be seen in the absence of lymph node resection in NSCLC patients with emphysema., Conclusion: A thorough evaluation and removal of the hilar and mediastinal lymph nodes may prove useful in determining the cancer stage and assessing the need for further treatment, thus enhancing the prognosis of patients with stage IA NSCLC., (Copyright © 2025 Journal of Cancer Research and Therapeutics.)

Background: Cryoablation induces antitumor immune responses. Spatial transcriptomic landscape technology has been used to determine the micron-level panoramic transcriptomics of tissue slices in situ., Methods: The effects of cryoablation on the immune microenvironment in non-small cell lung cancer (NSCLC) were explored by comparing the Whole Transcriptome Atlas (WTA) panel of immune cells before and after cryoablation using the spatial transcriptomic landscape., Results: The bioinformatics analysis showed that cryoablation significantly affected the WTA of immune cells, particularly genes related to cellular components, biological processes, molecular functions, proliferation and migration, and cytokine-cytokine receptor interaction signaling pathways., Conclusions: The findings of this study suggest that cryoablation significantly impacts the biological functions of immune cells in the tumor microenvironment of NSCLC through multiple mechanisms., (Copyright © 2025 Journal of Cancer Research and Therapeutics.)