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Recently, intelligent analysis of lung nodules with the assistant of computer aided diagnosis (CAD) techniques can improve the accuracy rate of lung cancer diagnosis. However, existing CAD systems and pulmonary datasets mainly focus on Computed Tomography (CT) images from one single period, while ignoring the cross spatio-temporal features associated with the progression of nodules contained in imaging data from various captured periods of lung cancer. If the evolution patterns of nodules across various periods in the patients' CT sequences can be explored, it will play a crucial role in guiding the precise screening identification of lung cancer. Therefore, a cross spatio-temporal lung nodule dataset with pathological information for nodule identification and diagnosis is constructed, which contains 317 CT sequences and 2,295 annotated nodules from 109 patients. This comprehensive database is intended to drive research in the field of CAD towards more practical and robust methods, and also contribute to the further exploration of precision medicine related field. To ensure patient confidentiality, we have removed sensitive information from the dataset., (© 2024. The Author(s).)

Lung cancer has emerged as a major global public health concern. With growing public interest in lung cancer, online searches for related information have surged. However, a comprehensive evaluation of the credibility, quality, and value of lung cancer-related videos on digital media platforms remains unexamined. This study aimed to assess the informational quality and content of lung cancer-related videos on Douyin and Bilibili. A total of 200 lung cancer-related videos that met the criteria were selected from Douyin and Bilibili for evaluation and analysis. The first step involved recording and analyzing the basic information provided in the videos. Subsequently, the source and type of content for each video were identified. All videos' educational content and quality were then evaluated using JAMA, GQS, and Modified DISCERN. Douyin videos were found to be more popular in terms of likes, comments, favorites, and shares, whereas Bilibili videos were longer in duration (P < .001). The majority of video content on both platforms comprised lung cancer introductions (31/100, 31%), with medical professionals being the primary source of uploaded videos (Douyin, n = 55, 55%; Bilibili, n = 43, 43%). General users on Douyin scored the lowest on the JAMA scale, whereas for-profit businesses scored the highest (2.50 points). The results indicated that the videos' informational quality was insufficient. Videos from science communications and health professionals were deemed more reliable regarding completeness and content quality compared to videos from other sources. The public should exercise caution and consider the scientific validity when seeking healthcare information on short video platforms., (© 2024. The Author(s).)

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI) approved for patients with EGFR T790M resistance mutations as first- or second-line treatment of EGFR-positive patients. Resistance to Osimertinib will inevitably develop, and the underlying mechanisms are largely unknown. In this study, we discovered that acquired resistance to Osimertinib is associated with abnormal DNA damage response (DDR) in lung adenocarcinoma cells. We discovered that the polycomb protein Lethal(3) Malignant Brain Tumor-Like Protein 1 (L3MBTL1) regulates chromatin structure, thereby contributing to DDR and Osimertinib resistance. EGFR oncogene inhibition reduced L3MBTL1 ubiquitination while stabilizing its expression in Osimertinib-resistant cells. L3MBTL1 reduction and treatment with Osimertinib significantly inhibited DDR and proliferation of Osimertinib-resistant lung cancer cells in vitro and in vivo. L3MBTL1 binds throughout the genome and plays an important role in EGFR-TKI resistance. It also competes with 53BP1 for H4K20Me2 and inhibits the development of drug resistance in Osimertinib-resistant lung cancer cells in vitro and in vivo. Our findings suggest that L3MBTL1 inhibition is a novel approach to overcoming EGFR-TKI-acquired resistance., (© 2024. The Author(s).)

Non-small cell lung cancer (NSCLC) patients infected with COVID-19 experience much worse prognosis. However, the specific mechanisms behind this phenomenon remain unclear. We conducted a multicentre study, collecting surgical tissue samples from a total of 36 NSCLC patients across three centres to analyse. Among the 36 lung cancer patients, 9 were infected with COVID-19. COVID-19 infection (HR = 21.62 [1.58, 296.06], p = 0.021) was an independent risk factor of progression-free survival (PFS). Analysis of RNA-seq data of these cancer tissues demonstrated significantly higher expression levels of cuproptosis-associated genes in COVID-19-infected lung cancer patients. Using Lasso regression and Cox regression analysis, we identified 12 long noncoding RNAs (lncRNA) regulating cuproptosis. A score based on these lncRNA were used to divide patients into high-risk and low-risk groups. The results showed that the high-risk group had lower overall survival and PFS compared to the low-risk group. Furthermore, Tumor Immune Dysfunction and Exclusion (TIDE) database revealed that the high-risk group benefited more from immunotherapy. Drug sensitivity analysis identified cetuximab and gefitinib as potentially effective treatments for the high-risk group. Cuproptosis plays a significant role NSCLC patients infected with COVID-19. Promisingly, cetuximab and gefitinib have shown potential effectiveness for managing these patients., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Lung cancer is a prevalent and severe form of malignant tumors worldwide. tRF-Leu-CAG, a recently discovered non-coding single-stranded small RNA derived from transfer RNA, has sparked interest in exploring its biological functions and potential molecular mechanisms in lung cancer., Methods: The abundance of tRF-Leu-CAG was measured via quantitative real-time polymerase chain reaction (qRT-PCR) in 96 sets of lung cancer tissue samples obtained from clinical patients. Subsequently, both in vivo and in vitro experiments were conducted to validate the biological functions of tRF-Leu-CAG in lung cancer. Furthermore, an exploration of the potential target genes of tRF-Leu-CAG and its association with autophagy and drug resistance in lung cancer was undertaken., Results: Our analysis revealed a significant upregulation of tRF-Leu-CAG in non-small cell lung cancer (NSCLC) tissues. Additionally, we observed that heightened expression of tRF-Leu-CAG significantly augmented the proliferation and migration of NSCLC cells, facilitated cell cycle progression, and suppressed apoptosis. Furthermore, we identified transcription elongation factor A3 (TCEA3) as a direct target gene of tRF-Leu-CAG. TCEA3 inhibited the proliferation and migration of NSCLC, and tRF-Leu-CAG promoted the proliferation and migration of NSCLC by mediating the silencing of TCEA3. Moreover, we demonstrated that the augmentation of paclitaxel resistance by tRF-Leu-CAG was contingent on autophagy. Finally, tRF-Leu-CAG notably accelerated tumor growth and promoted the process of epithelial-mesenchymal transition (EMT) in vivo., Conclusions: tRF-Leu-CAG promotes NSCLC tumor growth and metastasis by targeting TCEA3 and promotes paclitaxel resistance by enhancing cellular autophagy. These results provide potentially effective targets and therapeutic options for the clinical treatment of NSCLC., (© 2024 John Wiley & Sons Ltd.)

Objectives: The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types; however, its precise role within the context of lung adenocarcinoma (LUAD) remains elusive. This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways., Methods: Utilizing bioinformatics methodologies, we explored the differential expression of NCAPD2 between normal and tumor samples, along with its correlations with clinical-pathological characteristics, survival prognosis, and immune infiltration., Results: In the TCGA-LUAD dataset, tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples ( p < 0.001). Clinically, higher NCAPD2 expression was notably associated with advanced T, N, and M stages, pathologic stage, gender, smoking status, and diminished overall survival (OS). Moreover, differentially expressed genes (DEGs) associated with NCAPD2 were predominantly enriched in pathways related to cell division. Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells, naïve CD4+ T cells, activated memory CD4+ T cells, and M1 macrophages. In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cell cycle progression., Conclusions: In summary, NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD., Competing Interests: The authors declare that there is no possible conflict of interest., (© 2024 The Authors.)

Background: Activator protein-1 (AP-1) represents a transcription factor family that has garnered growing attention for its extensive involvement in tumor biology. However, the roles of the AP-1 family in the evolution of lung cancer remain poorly characterized. FBJ Murine Osteosarcoma Viral Oncogene Homolog B (FOSB), a classic AP-1 family member, was previously reported to play bewilderingly two-polarized roles in non-small cell lung cancer (NSCLC) as an enigmatic double-edged sword, for which the reasons and significance warrant further elucidation., Methods and Results: Based on the bioinformatics analysis of a large NSCLC cohort from the TCGA database, our current work found the well-known tumor suppressor gene TP53 served as a key code to decipher the two sides of FOSB - its expression indicated a positive prognosis in NSCLC patients harboring wild-type TP53 while a negative one in those harboring mutant TP53. By constructing a panel of syngeneically derived NSCLC cells expressing p53 in different statuses, the radically opposite prognostic effects of FOSB expression in NSCLC population were validated, with the TP53-R248Q mutation site emerging as particularly meaningful. Transcriptome sequencing showed that FOSB overexpression elicited diversifying transcriptomic landscapes across NSCLC cells with varying genetic backgrounds of TP53 and, combined with the validation by RT-qPCR, PREX1 (TP53-Null), IGFBP5 (TP53-WT), AKR1C3, and ALDH3A1 (TP53-R248Q) were respectively identified as p53-dependent transcriptional targets of FOSB. Subsequently, the heterogenous impacts of FOSB on the tumor biology in NSCLC cells via the above selective transcriptional targets were confirmed in vitro and in vivo. Mechanistic investigations revealed that wild-type or mutant p53 might guide FOSB to recognize and bind to distinct promoter sequences via protein-protein interactions to transcriptionally activate specific target genes, thereby creating disparate influences on the progression and prognosis in NSCLC., Conclusions: FOSB expression holds promise as a novel prognostic biomarker for NSCLC in combination with a given genetic background of TP53, and the unique interactions between FOSB and p53 may serve as underlying intervention targets for NSCLC., (© 2024. The Author(s).)

Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC., (© 2024. The Author(s).)

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile., (© 2024. The Author(s).)

Due to invasive and serial examinations of bioactive molecules, liquid biopsy (LB) has emerged as a rapid and reliable solution for early disease detection and monitoring. Developing portable devices with high specificity and sensitivity for LB is highly valuable. To realize a generalized approach to increase the sensitivity of LB, we developed an ultrasensitive diagnostic biochip based on the amplification of miRNA by recombinase polymerase amplification and the significant enhancement of fluorescence signals by photonic crystal (PC) materials. The PCs-RPA biochip has a detection limit as low as 0.24 aM, a wide linear range of 8 orders of magnitude, and excellent specificity. Such advantages realize the accurate detection of circulating miRNAs with very low content in clinical serum samples for the precise diagnosis of nonsmall cell lung cancer.

Background: Young lung cancer is a rare subgroup accounting for 5% of lung cancer. The aim of this study was to compare the causes of death (COD) among lung cancer patients of different age groups and construct a nomogram to predict cancer-specific survival (CSS) in young patients with advanced stage., Methods: Lung cancer patients diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and stratified into the young (18-45 years) and old (> 45 years) groups to compare their COD. Young patients diagnosed with advanced stage (IVa and IVb) from 2010 to 2015 were reselected and divided into training and validation cohorts (7:3). Independent prognostic factors were identified through the Fine-Gray's test and further integrated to the competing risk model. The area under the receiver operating characteristic curve (AUC), consistency index (C-index), and calibration curve were applied for validation., Results: The proportion of cancer-specific death (CSD) in young patients was higher than that in old patients with early-stage lung cancer (p < 0.001), while there was no difference in the advanced stage (p = 0.999). Through univariate and multivariate analysis, 10 variables were identified as independent prognostic factors for CSS. The AUC of the 1-, 3-, and 5-year prediction of CSS was 0.688, 0.706, and 0.791 in the training cohort and 0.747, 0.752, and 0.719 in the validation cohort. The calibration curves demonstrated great accuracy. The C-index of the competing risk model was 0.692 (95% CI: 0.636-0.747) in the young patient cohort., Conclusion: Young lung cancer is a distinct entity with a different spectrum of competing risk events. The construction of our nomogram can provide new insights into the management of young patients with lung cancer., (© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Immune checkpoint inhibitors provide a definite survival benefit for patients with driver-negative advanced non-small cell lung cancer (NSCLC), but predictors of efficacy are still lacking. There may be a relationship between immune inflammatory state and tumor immune response. We explored the relationship of serum neutrophil extracellular traps (NETs) with infiltrating cells in the tumor tissues of patients with NSCLC as well as their relationship with the therapeutic efficacy of programmed cell death protein 1 (PD-1) inhibitors. Serum myeloperoxidase (MPO)-double-stranded DNA (dsDNA) was detected as a marker of NET serum concentration. T cells were detected by immunohistochemical staining, and neutrophils were counted by MPO immunofluorescence staining. Of the 31 patients with NSCLC, a longer progression-free survival after PD-1 inhibitor treatment was associated with higher levels of CD3 + T cells, a lower neutrophil : CD3 + -T-cell ratio (NEU/CD3 + ) and lower neutrophil : CD8 + -T-cell ratio (NEU/CD8 + ) in tumor tissues. Patients with higher serum NETs were more likely to develop progressive disease after treatment (P = 0.003) and to have immune-related adverse events (IrAEs) as well as higher NEU/CD3 + and NEU/CD8 + . The combined model of serum NETs, CD8 + T cells, and tumor proportion score (TPS) significantly improved the prediction of PD-1 inhibitor efficacy [P = 0.033; area under the curve (AUC) = 0.881]. Our results indicate that serum NETs are effective predictors of PD-1 inhibitor response and reflect the tissue neutrophil-to-lymphocyte ratio and IrAE levels. The combined model of serum NETs, CD8 + T cells, and TPS is a powerful tool for predicting the efficacy of PD-1 inhibitor treatment in patients with NSCLC., (© 2024 Federation of European Biochemical Societies.)

Recently, Computer-Aided Diagnosis (CAD) systems have emerged as indispensable tools in clinical diagnostic workflows, significantly alleviating the burden on radiologists. Nevertheless, despite their integration into clinical settings, CAD systems encounter limitations. Specifically, while CAD systems can achieve high performance in the detection of lung nodules, they face challenges in accurately predicting multiple cancer types. This limitation can be attributed to the scarcity of publicly available datasets annotated with expert-level cancer type information. This research aims to bridge this gap by providing publicly accessible datasets and reliable tools for medical diagnosis, facilitating a finer categorization of different types of lung diseases so as to offer precise treatment recommendations. To achieve this objective, we curated a diverse dataset of lung Computed Tomography (CT) images, comprising 330 annotated nodules (nodules are labeled as bounding boxes) from 95 distinct patients. The quality of the dataset was evaluated using a variety of classical classification and detection models, and these promising results demonstrate that the dataset has a feasible application and further facilitate intelligent auxiliary diagnosis., (© 2024. The Author(s).)

Lung cancer is the top cause of cancer deaths globally. Advances in immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but their use in lung cancer has led to more side effects. This study examined if past pulmonary tuberculosis (TB) affects ICIs' effectiveness and safety in lung cancer treatment. We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022. We compared outcomes and side effects between patients with and without prior TB. Of 116 patients (40 with TB history, 76 without), prior TB didn't reduce treatment effectiveness but did increase severe side effects. Notably, older patients (≥ 65 years) faced a higher risk of severe side effects. Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs, stressing the need for careful monitoring and personalized care., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

This corrects the article published in the European Journal of Histochemistry 2014;58:2262. doi: 10.4081/ejh.2014.2262.

Background: With a considerable variety of cancer subtypes, Non-small cell lung cancer (NSCLC) poses a substantial threat to public health, affecting a large number of individuals and resulting in a high mortality rate. Circular RNA (circRNA) has been applied in various diseases, including cancers. This study aims to investigate the clinial significance and functional role of circPTP4A2 in NSCLC., Methods: The serum and tissue samples were collected for detecting circPTP4A2 expression in NSCLC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Actinomycin D was used to treat NSCLC cells to detect circPTP4A2 stability. The CCK-8 and Transwell assays were utilized to assess the effects of circPTP4A2 in NSCLC cells. The ELISA assay and cytotoxicity analysis were used to detect the roles of circPTP4A2 in immune escape., Results: The serum and tissue circPTP4A2 expression was upregulated in NSCLC. The high circPTP4A2 had a relatively high value in differentiating NSCLC patients from healthy individuals. The proliferation, invasion, and immune escape were repressed by circPTP4A2 knockdown., Conclusions: High circPTP4A2 has the potential to be a diagnostic biomarker in NSCLC. Silencing of circPTP4A2 receded the progression of NSCLC and enhanced antitumor immunity, which might provide potential targets and new ideas for improving the diagnosis and effect of immunotherapy in NSCLC patients., (© 2024. The Author(s).)

Lung cancer is a leading cause of cancer-related mortality globally, with a dismal 5-year survival rate, particularly for Lung Adenocarcinoma (LUAD). Mechanical changes within the tumor microenvironment, such as extracellular matrix (ECM) remodeling and fibroblast activity, play pivotal roles in cancer progression and metastasis. However, the specific impact of the basement membrane (BM) on the mechanical characteristics of LUAD remains unclear. This study aims to identify BM genes influencing internal mechanical stress in tumors, elucidating their effects on LUAD metastasis and therapy resistance, and exploring strategies to counteract these effects. Using Matrigel overlay and Transwell assays, we found that mechanical stress, mimicked by matrix application, augmented LUAD cell migration and invasion, correlating with ECM alterations and activation of the epithelial-mesenchymal transition (EMT) pathway. Employing machine learning, we developed the SVM&#95;Score model based on relevant BM genes, which accurately predicted LUAD patient prognosis and EMT propensity across multiple datasets. Lower SVM&#95;Scores were associated with worse survival outcomes, elevated cancer-related pathways, increased Tumor Mutation Burden, and higher internal mechanical stress in LUAD tissues. Notably, the SVM&#95;Score was closely linked to COL5A1 expression in myofibroblasts, a key marker of mechanical stress. High COL5A1 expression from myofibroblasts promoted tumor invasiveness and EMT pathway activation in LUAD cells. Additionally, treatment with Sorafenib, which targets COL5A1 secretion, attenuated the tumor-promoting effects of myofibroblast-derived COL5A1, inhibiting LUAD cell proliferation, migration, and enhancing chemosensitivity. In conclusion, this study elucidates the complex interplay between mechanical stress, ECM alterations, and LUAD progression. The SVM&#95;Score emerges as a robust prognostic tool reflecting tumor mechanical characteristics, while Sorafenib intervention targeting COL5A1 secretion presents a promising therapeutic strategy to mitigate LUAD aggressiveness. These findings deepen our understanding of the biomechanical aspects of LUAD and offer insights for future research and clinical applications., (© 2024. The Author(s).)

Background: Lung cancer is the second most common cancer with the highest mortality in the world. Calumenin as a molecular chaperone that not only binds various proteins within the endoplasmic reticulum but also plays crucial roles in diverse processes associated with tumor development. However, the regulatory mechanism of calumenin in lung adenocarcinoma remains elusive. Here, we studied the impact of calumenin on lung adenocarcinoma and explored possible mechanisms., Methods: 5-ethynyl-2'-deoxyuridine assay, colony formation, transwell and wound healing assays were performed to explore the effects of calumenin on the proliferation and migration of lung adenocarcinoma cells. To gain insights into the underlying mechanisms through which calumenin knockdown inhibits the migration and proliferation of lung adenocarcinoma, we performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis based on transcriptomics by comparing calumenin knockdown with normal A549 cells., Results: The mRNA and protein levels of calumenin in lung adenocarcinoma are highly expressed and they are related to an unfavorable prognosis in this disease. Calumenin enhances the proliferation and migration of A549 and H1299 cells. Gene Set Enrichment Analysis revealed that knockdown of calumenin in A549 cells significantly inhibited MYC and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling pathways while activating interferon signals, inflammatory signals, and p53 pathways. Ingenuity pathway analysis provided additional insights, indicating that the interferon and inflammatory pathways were prominently activated upon calumenin knockdown in A549 cells., Conclusions: The anti-cancer mechanism of calumenin knockdown might be related to the inhibition of MYC and KRAS signals but the activation of interferon signals, inflammatory signals and p53 pathways., (© 2024. The Author(s).)

Background: Determining the optimal energy layer (EL) for each field, under considering both dose constraints and delivery efficiency, is crucial to promoting the development of proton arc therapy (PAT) technology., Purpose: This study aimed to explore the feasibility and potential clinical benefits of utilizing machine learning (ML) technique to automatically select EL for each field in PAT plans of lung cancer., Methods: Proton Bragg peak position (BPP) was employed to characterize EL. The ground truth BPPs for each field were determined using the modified ELO-SPAT framework. Features in geometric, water-equivalent thicknesses (WET) and beamlet were defined and extracted. By analyzing the relationship between the extracted features and ground truth, a polynomial regression model with L2-norm regularization (Ridge regression) was constructed and trained. The performance of the regression model was reported as an error between the predictions and the ground truth. Besides, the predictions were used to make PAT plans (PAT&#95;PRED). These plans were compared with those using the ground truth BPPs (PAT&#95;TRUTH) and the mid-WET of the target volumes (PAT&#95;MID) in terms of relative biological effectiveness-weighted dose (RWD) distributions. One hundred ten patients with lung cancer, a total of 7920 samples, were enrolled retrospectively, with 5940 cases randomly selected as the training set and the remaining 1980 cases as the testing set. Nine patients (648 samples) were collected additionally to evaluate the regression model in terms of plan quality and robustness., Results: With regard to the prediction errors, the root mean squared errors and mean absolute errors between the ML-predicted and ground truth BPPs for the testing set were 9.165 and 6.572 mm, respectively, indicating differences of approximately two to three ELs. As for plan quality, the PAT&#95;TRUTH and PAT&#95;PRED plans performed similarly in terms of plan robustness, target coverage and organs at risk (OARs) protection, with differences smaller than 0.5 Gy(RBE). This trend was also observed for dose conformity and uniformity. The PAT&#95;MID plans produced the lowest robustness index and lowest doses to OARs, along with the highest heterogeneity index, indicating better protection for OARs, improved plan robustness, but compromised dose homogeneity. Additionally, for relatively small tumor sizes, the PAT&#95;MID plan demonstrated a notably poor dose conformity index., Conclusions: Within this cohort under investigation, our study demonstrated the feasibility of using ML technique to predict ELs for each field, offering a fast (within 2 s) and memory-efficient reduced way to select ELs for PAT plan., (© 2024 American Association of Physicists in Medicine.)

Purpose: This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer., Patients and Methods: Split-course hypo-RT and hypoboost combined with concurrent chemotherapy was administered at three dose levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL aimed to treat six patients. The MTFD was defined as the highest DL at which ≤2 patients of the six who were treated experienced treatment-related G3+ toxicity and ≤1 patient experienced G4+ toxicity within 12 months post-RT., Results: Eighteen patients were enrolled, with six patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rates were 94.4% and 83.3%, respectively., Conclusions: Utilizing the split-course hypo-RT and hypoboost approach, a fraction dose of 5 Gy to a total dose of 60 Gy, combined with concurrent chemotherapy and subsequent cICI, was well tolerated and yielded a promising objective response rate and survival outcomes., (©2024 American Association for Cancer Research.)

Objectives: Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low-dose computed tomography (LDCT) screening for the high-risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real-world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick-slice LDCT scanning., Methods: A total of 29 296 subjects who underwent low-dose thick-slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low-dose thin-slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups., Results: The positive rate of LDCT screening in the thin-slice scanning group was significantly higher than that in the thick-slice scanning group (20.1% vs. 14.4%, p < 0.001). In addition, the lung cancer detection rate in the thin-slice LDCT screening positive group was significantly higher than that in the thick-slice scanning group (78.0% vs. 52.9%, p < 0.001)., Conclusions: The screening positive rate of low-dose thin-slice CT scanning is higher and more early-stage lung cancer (IA1 stage) can be detected in the screen-positive group., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent in vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G 0 /G 1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis. Further RNA-seq analysis demonstrated that treatment of grifolin on A549 cells led to gene enrichment in MAPK, PI3K/Akt and NF-κB signaling pathways, all of which were inhibited by grifolin according to immunoblotting experiments. Further mechanistical studies disclosed that the expression of a key upstream protein KRAS was also blocked, and the cell death triggered by grifolin could be rescued by a RAS activator ML-099. Moreover, pretreatment of ML-099 on A549 cells could reverse the grifolin-induced downregulation of key proteins in the three aforementioned pathways. These findings indicate that grifolin could induce cell death in A549 cell line by inhibiting KRAS-mediated multiple signaling pathways., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Lung cancer is one of the most significant malignancies, with both high morbidity and mortality. CDK10 is closely related to cancer progression and metastasis. However, its role in lung cancer radioresistance demands further clarification. In this study, we demonstrated that CDK10 was downregulated in lung cancer tissues, and CDK10 expression level was associated with the clinical prognosis in lung cancer patients. We also found that silencing CDK10 promoted lung cancer cell proliferation, migration, and radioresistance. We further verified that silencing CDK10 facilitated the activation of JNK/c-Jun signaling, and c-Jun depletion could reverse the effects of CDK10 knockdown in lung cancer cells. Our findings revealed that CDK10 plays an important role in cell growth and radioresistance by inhibiting JNK/c-Jun signaling pathway in lung cancer. Therefore, CDK10 might be a promising therapeutic target in lung cancer. [BMB Reports 2024; 57(7): 336-341].

Introduction: Cancer cachexia is a complex problem characterized by weight loss due to skeletal muscle and adipose tissue reduction. The purpose of this meta-analysis is to examine the association between cancer cachexia and adverse outcomes in patients with non-small cell lung cancer (NSCLC)., Methods: A comprehensive search was conducted in the PubMed, Web of Science, and Embase databases from their inception to January 15, 2024. Retrospective or prospective studies that investigated the cancer cachexia as a predictor of overall survival (OS), progression-free survival (PFS), overall response rate (ORR), or disease control rate (DCR) in NSCLC patients were included in this analysis., Results: Sixteen studies, comprising 5919 NSCLC patients, were identified. The pooled prevalence of cachexia in NSCLC patients was 39%, with individual studies reporting rates ranging from 19% to 63.8%. A meta-analysis using a random effects model showed that cachexia was associated with reduced OS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.54-2.21) and PFS (HR 1.49; 95% CI 1.27-1.73). Subgroup analysis indicated that cancer cachexia significantly predicted OS, regardless of study design, NSCLC subtypes, cancer stage, definitions of cachexia, or follow-up duration. However, there was no clear association between cancer cachexia and ORR or DCR., Conclusions: Cancer cachexia emerges is a negative prognostic factor for OS and PFS in NSCLC patients. Assessing cancer cachexia can improve risk classification for survival outcomes in this patient population., Competing Interests: Conflict of interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Lung cancer is the most common malignant tumor. In the present study, we identified a long non-coding RNA (lncRNA) AC100826.1 (simplify to Lnc1), which was highly expressed in non-small cell lung cancer (NSCLC) tissues compared with the paracancerous tissues. We also observed the critical role of Lnc1 in regulating the metastasis ability of NSCLC cells., Methods: RNA sequencing was performed to detect differential expression levels of lncRNAs in NSCLC tissues and its paracancerous tissues. Effects of Lnc1 on cell proliferation, invasion, and migration were determined by CCK-8, transwell and scratch assays. The xenograft experiment confirmed the effect of Lnc1 on NSCLC cells proliferation and migration abilities in vivo. RT-qPCR and western blots were performed to determine the expression levels of mRNAs and proteins., Results: The expression level of Lnc1 was related to multiple pathological results, knockdown of Lnc1 can inhibit the proliferation and metastasis abilities of NSCLC cells. silencing phospholipase C, β1(PLCB1) can reverse the promoting effects of overexpression Lnc1 on NSCLC cells proliferation and migration abilities. In addition, the Rap1 signaling pathway was implicated in the regulation of Lnc1 in NSCLC metastasis., Conclusion: Our results suggest that Lnc1 regulated the metastatic ability of NSCLC cells through targeting the PLCB1/Rap1 signal pathway., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Sarcandra glabra (S. glabra), a traditional Chinese medicine (TCM), has demonstrated significant anticancer activity; however, the underlying mechanisms have not yet been fully elucidated., Purpose: This study aimed to investigate the effects of S. glabra on lung cancer and to explore its underlying mechanisms., Methods: The chemical profile of S. glabra was analyzed via ultrahigh-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). The effects of S. glabra on the viability, proliferation, apoptosis, migration, and invasion of lung cancer cells were assessed via CCK8, colony formation, flow cytometry, scratch, and Transwell assays. In vivo anticancer activity was evaluated in an LLC mouse model. Proteomic analysis was performed to identify key molecules and pathways in S. glabra-treated LLC cells. The expression of ferroptotic proteins and associated cellular events were examined via western blotting, ROS production, iron accumulation, and lipid peroxidation assays. Immune modulation in tumor-bearing mice was evaluated by detecting immune cells and cytokines in the peripheral blood and tumor tissue., Results: Our analysis quantified 1997 chemical markers in S. glabra aqueous extracts. S. glabra inhibited the viability and proliferation of lung cancer cells and induced cell cycle arrest and apoptosis. Scratch and Transwell assays demonstrated that S. glabra suppressed the migration and invasion of lung cancer cells. Oral administration of S. glabra significantly inhibited tumor growth in LLC tumor-bearing mice. Proteomic analysis revealed that S. glabra upregulated the expression of the HMOX1 protein and activated the ferroptosis pathway. Consistent with these findings, we found that S. glabra triggered ferroptosis in lung cancer cells, as evidenced by the upregulation of HMOX1, downregulation of GPX4 and ferritin light chain proteins, iron accumulation, increased ROS production, and lipid peroxidation. Furthermore, S. glabra demonstrated immunostimulatory properties in LLC tumor-bearing mice, leading to increased populations of immune cells (NK cells) and elevated cytokine levels (IL-2)., Conclusion: This study is the first to demonstrate that S. glabra induces ferroptosis in lung cancer cells by regulating HMOX1, GPX4, and FTL. These findings provide a robust scientific basis for the clinical application of S. glabra in lung cancer treatment., 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 GmbH. All rights reserved.)

Purpose: As a non-invasive coronary functional examination, coronary computed tomography angiography (CCTA)-derived fractional flow reserve (CT-FFR) showed predictive value in several non-cardiac surgeries. This study aimed to evaluate the predictive value of CT-FFR in lung cancer surgery., Method: We retrospectively collected 227 patients from January 2017 to June 2022 and used machine learning-based CT-FFR to evaluate the stable coronary artery disease (CAD) patients undergoing lung cancer surgery. The major adverse cardiac event (MACE) was defined as perioperative myocardial injury (PMI), myocardial infarction, heart failure, atrial and ventricular arrhythmia with hemodynamic disorder, cardiogenic shock and cardiac death. The multivariate logistic regression analysis was performed to identify risk factors for MACE and PMI. The discriminative capacity, goodness-of-fit, and reclassification improvement of prediction model were determined before and after the addition of CT-FFR≤0.8., Results: The incidence of MACE was 20.7 % and PMI was 15.9 %. CT-FFR significantly outperformed CCTA in terms of accuracy for predicting MACE (0.737 vs 0.524). In the multivariate regression analysis, CT-FFR≤0.8 was an independent risk factor for both MACE [OR=10.77 (4.637, 25.016), P<0.001] and PMI [OR=8.255 (3.372, 20.207), P<0.001]. Additionally, we found that the performance of prediction model for both MACE and PMI improved after the addition of CT-FFR., Conclusions: CT-FFR can be used to assess the risk of perioperative MACE and PMI in patients with stable CAD undergoing lung cancer surgery. It adds prognostic information in the cardiac evaluation of patients undergoing lung cancer surgery., 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.)

Lung adenocarcinoma (LUAC) as the most common lung cancer, and its incidence is increasing. Complement factor B (CFB) is an important factor in the alternative complement pathway. CFB has been reported to be involved in the progression of many cancers, including in pancreatic cancer, cutaneous squamous cell carcinoma, and nasopharyngeal carcinoma, but the function and molecular mechanism of CFB in LUAC remains unclear. The present study aimed to explore the role of CFB in LUAC malignant progression. In our previous study, we found that CFB was downregulated expression in LUAC clinical samples. Here, we firstly detected the cell function in vitro. Cell proliferation and migration were increased, while cell apoptosis and cell cycle arrest were suppressed after CFB knockdown. Overexpression of CFB repressed the malignant progression of LUAC in vitro. Besides, in vivo experiments revealed that upregulation of CFB inhibited tumor growth and Ki67 expression. Additionally, our data indicated that CFB negatively regulated Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, upregulation of CFB inhibited the progression of LUAC was reversed by Ras/MAPK pathway activators (ML-098 or C16-PAF). Our study uncovered that CFB acts as a tumor suppressor repressed tumorigenesis of LUAC through inhibiting the Ras/MAPK pathway, suggesting that CFB may be a potential biomarker and therapeutic target for LUAC., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

There is a paucity of comprehensive knowledge pertaining to the underlying mechanisms leading to gefitinib resistance in individuals diagnosed NSCLC harboring EGFR-sensitive mutations who inevitably develop resistance to gefitinib treatment within six months to one year. In our preceding investigations, we have noted a marked upregulation of IGFBP2 in the neoplastic tissues of NSCLC, predominantly in the periphery of the tissue, implying its plausible significance in NSCLC. Consequently, in the current research, we delved into the matter and ascertained the molecular mechanisms that underlie the participation of IGFBP2 in the emergence of gefitinib resistance in NSCLC cells. Firstly, the expression of IGFBP2 in the bronchoalveolar lavage fluid and lung cancer tissues of 20 NSCLC patients with gefitinib tolerance was found to be significantly higher than that of non-tolerant patients. Furthermore, in vitro and in vivo experiments demonstrated that IGFBP2 plays a significant role in the acquisition of gefitinib resistance. Mechanistically, IGFBP2 can activate STAT3 to enhance the transcriptional activity of CXCL1, thereby increasing the intracellular expression level of CXCL1, which contributes to the survival of lung cancer cells in the gefitinib environment. Additionally, we identified ITGA5 as a key player in IGFBP2-mediated gefitinib resistance, but it does not function as a membrane receptor in the process of linking IGFBP2 to intracellular signaling transduction. In conclusion, this study demonstrates the promoting role and mechanism of IGFBP2 in acquired gefitinib resistance caused by non-EGFR secondary mutations, suggesting the potential of IGFBP2 as a biomarker for gefitinib resistance and a potential intervention target., (© 2024. The Author(s).)

Background: Whether programmed cell death-1/ligand-1 (PD-1/PD-L1) blockade-based neoadjuvant treatment may benefit locally advanced oncogene-mutant non-small cell lung cancer (NSCLC) patients remains controversial. This retrospective study was designed to observe the efficacy and safety of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy versus chemotherapy and corresponding tyrosine kinase inhibitors (TKIs) in patients with resectable oncogene-positive NSCLC., Methods: Patients with potential resectable NSCLC harbouring oncogene alterations who had received neoadjuvant treatment were retrospectively recruited, and an oncogene-negative cohort of patients who received neoadjuvant PD-(L)1 blockade-based neoadjuvant treatment was reviewed for comparison during the same period. The primary aim was to observe the treatment efficacy and event-free survival (EFS) of these agents. Safety profile, molecular target, and immunologic factor data, including PD-L1 expression and tumour mutational burden (TMB), were also obtained., Results: A total of 46 patients were recruited. Thirty-one of them harboured oncogene alterations, including EGFR, KRAS, ERBB2, ROS1, MET, RET, ALK, and FGFR3 alterations. Among the oncogene-positive patients, 18 patients received neoadjuvant PD-(L)1 blockade immunotherapy plus chemotherapy (oncogene-positive IO group), 13 patients were treated with neoadjuvant chemotherapy and/or corresponding TKIs or TKIs alone (oncogene-positive chemo/TKIs group), and the other 15 patients were oncogene negative and received neoadjuvant PD-(L)1 blockade plus chemotherapy (oncogene-negative IO group). The pathological complete response (pCR) and major pathological response (MPR) rates were 22.2% (4 of 18) and 44.4% (8 of 18) in the oncogene-positive IO group, 0% (P = 0.120) and 23.1% (3 of 13) (P = 0.276) in the oncogene-positive chemo/TKIs group, and 46.7% (7 of 15) (P = 0.163) and 80.0% (12 of 15) (P = 0.072) in the oncogene-negative IO group, respectively. By the last follow-up, the median EFS time had not reached in the oncogene-positive IO group, and was 29.5 months in the oncogene-positive chemo/TKIs group and 38.4 months in the oncogene-negative IO group., Conclusion: Compared with chemotherapy/TKIs treatment, neoadjuvant treatment with PD-(L)1 blockade plus platinum-based chemotherapy was associated with higher pCR/MPR rates in patients with partially resectable oncogene-mutant NSCLC, while the pCR/MPR rates were lower than their oncogene-negative counterparts treated with PD-(L)1 blockade-based treatment. Specifically, oncogene alteration types and other predictors of response to immunotherapy should be taken into account in clinical practice., (© 2024. The Author(s).)

Conducting this research contributes to a deeper understanding of the correlation between atmospheric environmental quality and lung cancer incidence, and provides the scientific basis for formulating effective environmental protection and lung cancer prevention and control strategies. Lung cancer incidence in China has strong spatial variation. However, few studies have systematically revealed the characteristics of the spatial variation in lung cancer incidence, and have explained the causes of this spatial variation in lung cancer incidence from the perspectives of multiple components of the atmospheric environment to explain this spatial variation in lung cancer incidence. To address research limitations, we first analyze the spatial variation and spatial correlation characteristics of lung cancer incidence in China. Then, we build a spatial regression model using GeoDa software with lung cancer incidence as the dependent variable, five atmospheric environment factors-particulate matter 2.5 (PM2.5) concentration, temperature, atmospheric pressure, and elevation as explanatory variables, and four socio-economic characteristics as control variables to systematically analyze the influence and intensity of these factors on lung cancer incidence. The results show that lung cancer incidence in China has apparent changes in geographical and spatial unevenness, and spatial autocorrelation characteristics. In China, the lung cancer incidence is relatively high in Northeast China, while some areas of high lung cancer incidence still exist in Central China, Southwest China and South China, although the overall lung cancer incidence is relatively low. The atmospheric environment significantly affects lung cancer incidence. Different elements of the atmospheric environment vary in the direction and extent of their influence on the development of lung cancer. A 1% increase in PM2.5 concentration is associated with a level of 0.002975 increase in lung cancer incidence. Atmospheric pressure positively affects lung cancer incidence, and an increase in atmospheric pressure by 1% increases lung cancer incidence by a level of 0.026061. Conversely, a 1% increase in temperature is linked to a level of 0.006443 decreases in lung cancer incidence, and a negative correlation exists between elevation and lung cancer incidence, where an increase in elevation by 1% correlates with a decrease in lung cancer incidence by a level of 0.000934. The core influencing factors of lung cancer incidence in the seven geographical divisions of China exhibit variations. This study facilitates our understanding of the spatial variation characteristics of lung cancer incidence in China on a finer scale, while also offering a more diverse perspective on the impact of the atmospheric environment on lung cancer incidence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC., (© 2024. The Author(s).)

Background: Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy., Methods: We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike's information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model's performance., Results: The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9., Conclusions: Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN., (© 2024. The Author(s).)

Purpose: Lung adenocarcinoma (LUAD) is a prevalent malignant tumor worldwide, with high incidence and mortality rates. However, there is still a lack of specific and sensitive biomarkers for its early diagnosis and targeted treatment. Disulfidptosis is a newly identified mode of cell death that is characteristic of disulfide stress. Therefore, exploring the correlation between disulfidptosis-related long non-coding RNAs (DRGs-lncRNAs) and patient prognosis can provide new molecular targets for LUAD patients., Methods: The study analysed the transcriptome data and clinical data of LUAD patients in The Cancer Genome Atlas (TCGA) database, gene co-expression, and univariate Cox regression methods were used to screen for DRGs-lncRNAs related to prognosis. The risk score model of lncRNA was established by univariate and multivariate Cox regression models. TIMER, CIBERSORT, CIBERSORT-ABS, and other methods were used to analyze immune infiltration and further evaluate immune function analysis, immune checkpoints, and drug sensitivity. Real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of DRGs-lncRNAs in LUAD cell lines., Results: A total of 108 lncRNAs significantly associated with disulfidptosis were identified. A prognostic model was constructed by screening 10 lncRNAs with independent prognostic significance through single-factor Cox regression analysis, LASSO regression analysis, and multiple-factor Cox regression analysis. Survival analysis of patients through the prognostic model showed that there were obvious survival differences between the high- and low-risk groups. The risk score of the prognostic model can be used as an independent prognostic factor independent of other clinical traits, and the risk score increases with stage. Further analysis showed that the prognostic model was also different from tumor immune cell infiltration, immune function, and immune checkpoint genes in the high- and low-risk groups. Chemotherapy drug susceptibility analysis showed that high-risk patients were more sensitive to Paclitaxel, 5-Fluorouracil, Gefitinib, Docetaxel, Cytarabine, and Cisplatin. Additionally, RT-PCR analysis demonstrated differential expression of DRGs-lncRNAs between LUAD cell lines and the human bronchial epithelial cell line., Conclusions: The prognostic model of DRGs-lncRNAs constructed in this study has certain accuracy and reliability in predicting the survival prognosis of LUAD patients, and provides clues for the interaction between disulfidptosis and LUAD immunotherapy.

Background: Undetermined lung nodules are common in locally advanced rectal cancer (LARC) and lack precise risk stratification. This study aimed to develop a radiomic-based score (Rad-score) to distinguish metastasis and predict overall survival (OS) in patients with LARC and lung nodules., Methods: Retrospective data from two institutions (July 10, 2006-September 24, 2015) was used to develop and validate the Rad-score for distinguishing lung nodule malignancy. The prognostic value of the Rad-score was investigated in LARC cohorts, leading to the construction and validation of a clinical and radiomic score (Cli-Rad-score) that incorporates both clinical and radiomic information for the purpose of improving personalized clinical prognosis prediction. Descriptive statistics, survival analysis, and model comparison were performed to assess the results., Results: The Rad-score demonstrated great performance in distinguishing malignancy, with C-index values of 0.793 [95% CI: 0.729-0.856] in the training set and 0.730 [95% CI: 0.666-0.874] in the validation set. In independent LARC cohorts, Rad-score validation achieved C-index values of 0.794 [95% CI: 0.737-0.851] and 0.747 [95% CI: 0.615-0.879]. Regarding prognostic prediction, Rad-score effectively stratified patients. Cli-Rad-score outperformed the clinicopathological information alone in risk stratification, as evidenced by significantly higher C-index values (0.735 vs. 0.695 in the internal set and 0.618 vs. 0.595 in the external set)., Conclusions: CT-based radiomics could serve as a reliable and powerful tool for lung nodule malignancy distinction and prognostic prediction in LARC patients. Rad-score predicts prognosis independently. Incorporation of Cli-Rad-score significantly enhances the persionalized clinical prognostic capacity in LARC patients with lung nodules., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Radio-photothermal therapy is an effective modality for cancer treatment. To overcome the radio-resistance in the hypoxic microenvironment and improve the sensitivity of radiotherapy, metal nanoparticles, and radio-photothermal therapy are widely used in the research of improving the curative effect and reducing the side effects of radiotherapy. Here, we developed red blood membrane camouflaging bismuth nanoflowers (RBCM-BNF) with outstanding physiological stability and biodegradability for lung tumours. In vitro data proved that the RBCM-BNF had the greatest cancer cell-killing ability combined with X-ray irradiation and photo-thermal treatment. Meanwhile, in vivo studies revealed that RBCM-BNF can alleviate the hypoxic microenvironment and promote tumour cell apoptosis by inhibiting HIF-1α expression and increasing caspase-3 expression. Therefore, RBCM-BNF had a good radio-sensitising effect and might be a promising biomimetic nanoplatform as a therapeutic target for cancer.

DNA methylation, an epigenetic mechanism that alters gene expression without changing DNA sequence, is essential for organism development and key biological processes like genomic imprinting and X-chromosome inactivation. Despite tremendous efforts in DNA methylation research, accurate quantification of cytosine methylation remains a challenge. Here, a single-base methylation quantification approach is introduced by weighting methylation of consecutive CpG sites (Wemics) in genomic regions. Wemics quantification of DNA methylation better predicts its regulatory impact on gene transcription and identifies differentially methylated regions (DMRs) with more biological relevance. Most Wemics-quantified DMRs in lung cancer are epigenetically conserved and recurrently occurred in other primary cancers from The Cancer Genome Atlas (TCGA), and their aberrant alterations can serve as promising pan-cancer diagnostic markers. It is further revealed that these detected DMRs are enriched in transcription factor (TF) binding motifs, and methylation of these TF binding motifs and TF expression synergistically regulate target gene expression. Using Wemics on epigenomic-transcriptomic data from the large lung cancer cohort, a dozen novel genes with oncogenic potential are discovered that are upregulated by hypomethylation but overlooked by other quantification methods. These findings increase the understanding of the epigenetic mechanism by which DNA methylation regulates gene expression., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Lung cancer, with high morbidity and mortality, is the commonest respiratory system neoplasm, which seriously endangers the life safety of patients. In this study, the effect of PRPS2 on cell progression was preliminarily investigated., Methods: Immunohistochemical staining, western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to verify the expression level of PRPS2 in lung cancer. Lung cancer cell lines with stable downregulation of PRPS2 were constructed in A549 cells and NCIH460 cells. The function of PRPS2 silencing on the proliferation ability was verified by the EdU and cell colony formation experiment. Scratch and transwell tests were conducted to verify the role of PRPS2 silencing on the migratory and invasive ability of cells. The impact of PRPS2 silencing on cell apoptosis and cell cycle was verified by flow cytometry test. The effects of PRPS2 silencing on apoptosis-associated proteins were assessed by western blot assay. The function of PRPS2 silencing on tumor growth in vivo was studied through xenograft tumor experiment., Results: In comparison with normal tissues, PRPS2 was upregulated in lung cancer tissues. PRPS2 knockdown notably hindered the migratory ability, invasive ability and proliferation, but accelerated cell apoptosis. In vivo experiments confirmed that PRPS2 silencing blocked the growth of transplanted tumors., Conclusion: In lung cancer, PRPS2 silencing suppressed the malignant progression, indicating that PRPS2 might be a novel biomarker for lung cancer treatment and diagnosis., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Introduction: Lung cancer's high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities and significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system with near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded with R837 and cisplatin (DDP), encapsulated within a temperature-sensitive hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), we administered in situ injections of MDR@SHDS into tumor tissues combined with photothermal therapy (PTT). The immune adjuvant R837 enhances dendritic cell (DC) maturation and tumor cell phagocytosis, while PTT induces tumor cell apoptosis and necrosis by converting light energy into heat energy., Methods: Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, and near-infrared thermography. In vitro experiments assessed Lewis cell proliferation and apoptosis using CCK-8, Edu, and TUNEL assays. In vivo experiments on C57 mouse Lewis transplant tumors evaluated the photothermal effect via near-infrared thermography and assessed DC maturation and CD4+/CD8+ T cell ratios using flow cytometry. The in vivo anti-tumor efficacy of MDR@SHDS was confirmed by tumor growth curve recording and HE and TUNEL staining of tumor sections., Results: The hydrogel exhibited excellent temperature sensitivity, controlled release properties, and high biocompatibility. In vitro experiments revealed that MDR@SHDS combined with PTT had a greater inhibitory effect on tumor cell proliferation compared to MDR@SHD alone. Combining local immunotherapy, chemotherapy, and PTT yielded superior anti-tumor effects than individual treatments., Conclusion: MDR@SHDS, with its simplicity, biocompatibility, and enhanced anti-tumor effects in combination with PTT, presents a promising therapeutic approach for lung cancer treatment, offering potential clinical utility., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ma et al.)

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P ＜0.001; 77.78% vs 16.84% for bone metastasis, P ＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P =0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P =0.002; 44.83% vs 20.23 % for bone metastasis, P =0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P =0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P =0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P =0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P =0.019; 8.03 months vs 19.50 months for OS, P =0.019, P =0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P =0.004; 11.2 months vs 20.60 months for OS, P =0.019). Multivariate analysis showed that disease stage ( HR =2.806, 95% CI: 1.499-5.251, P =0.001) and DTCs quantity detected by SE-iFISH ( HR =1.841, 95% CI: 1.095-3.095, P =0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR =2.538, 95% CI: 1.169-5.512, P =0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Introduction: Lung cancer, with the highest global mortality rate among cancers, presents a grim prognosis, often diagnosed at an advanced stage in nearly 70% of cases. Recent research has unveiled a novel mechanism of cell death termed disulfidptosis, which is facilitated by glucose scarcity and the protein SLC7A11., Methods: Utilizing the least absolute shrinkage and selection operator (LASSO) regression analysis combined with Cox regression analysis, we constructed a prognostic model focusing on disulfidptosis-related genes. Nomograms, correlation analyses, and enrichment analyses were employed to assess the significance of this model. Among the genes incorporated into the model, CHRNA5 was selected for further investigation regarding its role in LUAD cells. Biological functions of CHRNA5 were assessed using EdU, transwell, and CCK-8 assays., Results: The efficacy of the model was validated through internal testing and an external validation set, with further evaluation of its robustness and clinical applicability using a nomogram. Subsequent correlation analyses revealed associations between the risk score and infiltration of various cancer types, as well as oncogene expression. Enrichment analysis also identified associations between the risk score and pivotal biological processes and KEGG pathways. Our findings underscore the significant impact of CHRNA5 on LUAD cell proliferation, migration, and disulfidptosis., Conclusion: This study successfully developed and validated a robust prognostic model centered on disulfidptosis-related genes, providing a foundation for predicting prognosis in LUAD patients., 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 © 2024 Wang, Liu, Li, Zhang, Gong, Song, Wei, Hu and Li.)

Recent research highlights the significance of exosomes and long noncoding RNAs (lncRNAs) in cancer progression and drug resistance, but their role in lung adenocarcinoma (LUAD) is not fully understood. We analyzed 121 exosome-related (ER) mRNAs from the ExoBCD database, along with mRNA and lncRNA expression profiles of TCGA-LUAD using "DESeq2", "survival," "ConsensusClusterPlus," "GSVA," "estimate," "glmnet," "clusterProfiler," "rms," and "pRRophetic" R packages. This comprehensive approach included univariate cox regression, unsupervised consensus clustering, GSEA, functional enrichment analysis, and prognostic model construction. Our study identified 134 differentially expressed ER-lncRNAs, with 19 linked to LUAD prognosis. These ER-lncRNAs delineated two patient subtypes, one with poorer outcomes. Additionally, 286 differentially expressed genes were related to these ER-lncRNAs, 261 of which also correlated with LUAD prognosis. We constructed an ER-lncRNA-related prognostic model and calculated an ER-lncRNA-related risk score (ERS), revealing that a higher ERS correlates with poor overall survival in both the Meta cohort and two validation cohorts. The ERS potentially serves as an independent prognostic factor, and the prognostic model demonstrates superior predictive power. Notably, significant differences in the immune landscape were observed between the high- and low-ERS groups. Drug sensitivity analysis indicated varying responses to common chemotherapy drugs based on ERS stratification, with the high-ERS group showing greater sensitivity, except to rapamycin and erlotinib. Experimental validation confirmed that thymidine kinase 1 enhances lung cancer invasion, metastasis, and cell cycle progression. Our study pioneers an ER-lncRNA-related prognostic model for LUAD, proposing that ERS-based risk stratification could inform personalized treatment strategies to improve patient outcomes., (© 2024. The Author(s).)

CRTAC1, one of the pyroptosis-related genes, has been identified as a protective factor in certain kinds of cancer, such as gastric adenocarcinoma and bladder cancer. The study aimed to investigate the role of CRTAC1 in lung adenocarcinoma (LUAD). LUAD datasets were obtained from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), pyroptosis-related genes from GeneCard. Limma package used to find differentially expressed genes (DEGs), least absolute shrinkage and selection operator (LASSO) regression and weighted genes co-expression network analysis (WGCNA) to identify CRTAC1 as hub gene. CRTAC1 expression was confirmed in a real-world cohort using quantitative polymerase chain reaction (qPCR) and Western Blot (WB) analyses. Cellular experiments were conducted to investigate CRTAC1's potential oncogenic mechanisms. CRTAC1 mRNA expression was significantly lower in LUAD tissues (p < 0.05) and showed high accuracy in diagnosing LUAD. Reduced CRTAC1 expression was associated with a poor prognosis. Higher CRTAC1 expression correlated with increased immune cell infiltration. Individuals with high CRTAC1 expression showed increased drug sensitivity. Additionally, qPCR and WB analyses showed that CRTAC1 expression was lower in tumor tissue compared to adjacent normal tissue at both the RNA and protein levels. Upregulation of CRTAC1 significantly inhibited LUAD cell proliferation, invasion, and migration in cellular experiments. CRTAC1 has the potential to serve as a diagnostic and prognostic biomarker in LUAD., (© 2024. The Author(s).)

Background and Purpose: Recently, the emergence of immune checkpoint inhibitors has significantly improved the survival of patients with extensive-stage small cell lung cancer. However, not all patients can benefit from immunotherapy; therefore, there is an urgent need for precise predictive markers to screen the population for the benefit of immunotherapy. However, single markers have limited predictive accuracy, so a comprehensive predictive model is needed to better enable precision immunotherapy. The aim of this study was to establish a prognostic model for immunotherapy in ES-SCLC patients using basic clinical characteristics and peripheral hematological indices of the patients, which would provide a strategy for the clinical realization of precision immunotherapy and improve the prognosis of small cell lung cancer patients., Methods: This research retrospectively collected data from ES-SCLC patients treated with PD-1/PD-L1 inhibitors between March 1, 2019, and October 31, 2022, at Harbin Medical University Cancer Hospital. The study data was randomly split into training and validation sets in a 7:3 ratio. Variables associated with patients' overall survival were screened and modeled by univariate and multivariate Cox regression analyses. Models were presented visually via Nomogram plots. Model discrimination was evaluated by Harrell's C index, tROC, and tAUC. The calibration of the model was assessed by calibration curves. In addition, the clinical utility of the model was assessed using a DCA curve. After calculating the total risk score of patients in the training set, patients were stratified by risk using percentile partitioning. The Kaplan-Meier method was used to plot OS and PFS survival curves for different risk groups and response statuses at different milestone time points. Differences in survival time groups were compared using the chi-square test. Statistical analysis software included R 4.1.2 and SPSS 26., Results: This study included a total of 113 ES-SCLC patients who received immunotherapy, including 79 in the training set and 34 in the validation set. Six variables associated with poorer OS in patients were screened by Cox regression analysis: liver metastasis (P = 0.001), bone metastasis (P = 0.013), NLR < 2.14 (P = 0.005), LIPI assessed as poor (P < 0.001), PNI < 51.03 (P = 0.002), and LDH ≥ 146.5 (P = 0.037). A prognostic model for immunotherapy in ES-SCLC patients was constructed based on the above variables. The Harrell's C-index in the training and validation sets of the model was 0.85 (95% CI 0.76-0.93) and 0.88 (95% CI 0.76-0.99), respectively; the AUC values corresponding to 12, 18, and 24 months in the tROC curves of the training set were 0.745, 0.848, and 0.819 in the training set and 0.858, 0.904 and 0.828 in the validation set; the tAUC curves show that the overall tAUC is > 0.7 and does not fluctuate much over time in both the training and validation sets. The calibration plot demonstrated the good calibration of the model, and the DCA curve indicated that the model had practical clinical applications. Patients in the training set were categorized into low, intermediate, and high risk groups based on their predicted risk scores in the Nomogram graphs. In the training set, 52 patients (66%) died with a median OS of 15.0 months and a median PFS of 7.8 months. Compared with the high-risk group (median OS: 12.3 months), the median OS was significantly longer in the intermediate-risk group (median OS: 24.5 months, HR = 0.47, P = 0.038) and the low-risk group (median OS not reached, HR = 0.14, P = 0.007). And, the median PFS was also significantly prolonged in the intermediate-risk group (median PFS: 12.7 months, HR = 0.45, P = 0.026) and low-risk group (median PFS not reached, HR = 0.12, P = 0.004) compared with the high-risk group (median PFS: 6.2 months). Similar results were obtained in the validation set. In addition, we observed that in real-world ES-SCLC patients, at 6 weeks after immunotherapy, the median OS was significantly longer in responders than in non-responders (median OS: 19.5 months vs. 11.9 months, P = 0.033). Similar results were obtained at 12 weeks (median OS: 20.7 months vs 11.9 months, P = 0.044) and 20 weeks (median OS: 20.7 months vs 11.7 months, P = 0.015). Finally, we found that in the real world, ES-SCLC patients without liver metastasis (P = 0.002), bone metastasis (P = 0.001) and a total number of metastatic organs < 2 (P = 0.002) are more likely to become long-term survivors after receiving immunotherapy., Conclusion: This study constructed a new prognostic model based on basic patient clinical characteristics and peripheral blood indices, which can be a good predictor of the prognosis of immunotherapy in ES-SCLC patients; in the real world, the response status at milestone time points (6, 12, and 20 weeks) can be a good indicator of long-term survival in ES-SCLC patients receiving immunotherapy., (© 2024. The Author(s).)

The management of patients with advanced non-small cell lung cancer (NSCLC) presents significant challenges due to cancer cells' intricate and heterogeneous nature. Programmed cell death (PCD) pathways are crucial in diverse biological processes. Nevertheless, the prognostic significance of cell death in NSCLC remains incompletely understood. Our study aims to investigate the prognostic importance of PCD genes and their ability to precisely stratify and evaluate the survival outcomes of patients with advanced NSCLC. We employed Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), univariate and multivariate Cox regression analyses for prognostic gene screening. Ultimately, we identified seven PCD-related genes to establish the PCD-related risk score for the advanced NSCLC model (PRAN), effectively stratifying overall survival (OS) in patients with advanced NSCLC. Multivariate Cox regression analysis revealed that the PRAN was the independent prognostic factor than clinical baseline factors. It was positively related to specific metabolic pathways, including hexosamine biosynthesis pathways, which play crucial roles in reprogramming cancer cell metabolism. Furthermore, drug prediction for different PRAN risk groups identified several sensitive drugs explicitly targeting the cell death pathway. Molecular docking analysis suggested the potential therapeutic efficacy of navitoclax in NSCLC, as it demonstrated strong binding with the amino acid residues of C-C motif chemokine ligand 14 (CCL14), carboxypeptidase A3 (CPA3), and C-X3-C motif chemokine receptor 1 (CX3CR1) proteins. The PRAN provides a robust personalized treatment and survival assessment tool in advanced NSCLC patients. Furthermore, identifying sensitive drugs for distinct PRAN risk groups holds promise for advancing targeted therapies in NSCLC.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC., Competing Interests: Declaration of interests H.Z. is an employee and shareholder of GeneX Health Co., Ltd. (GeneX Health) and J.J.X. is a shareholder of GeneX Health. GeneX Health has submitted one patent regarding PTC culture (A method for the culture of primary lung cancer cells, ZL 202111135387.8)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Given the modest efficacy of docetaxel in advanced non-small cell lung cancer (NSCLC), this study assesses the therapeutic potential and safety profile of anlotinib in combination with docetaxel compared to docetaxel monotherapy as a second-line therapy for patients with advanced NSCLC., Materials and Methods: In this phase II study, patients with advanced NSCLC experiencing failure with first-line platinum-based regimens were randomized in a 1:1 ratio to receive either anlotinib plus docetaxel or docetaxel alone. Primary endpoint was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety as secondary endpoints., Results: A total of 83 patients were randomized. The combination of anlotinib and docetaxel significantly extended median PFS to 4.4 months compared to 1.6 months for docetaxel alone (hazard ratio [HR] = 0.38, 95 % confidence interval [CI]: 0.23-0.63, P = 0.0002), and also demonstrated superior ORR (32.5 % vs. 9.3 %, P = 0.0089) and DCR (87.5 % vs. 53.5 %, P = 0.0007). Median OS was observed at 12.0 months in the combination group vs. 10.9 months in the monotherapy group (HR = 0.82, 95 % CI: 0.47-1.43, P = 0.4803). For patients previously treated with immunotherapy, the median PFS was notably longer at 7.8 vs. 1.7 months (HR = 0.22, 95 % CI: 0.09-0.51, P = 0.0290). The incidence of grade ≥ 3 treatment-related adverse events, predominantly leukopenia (15.0 % vs. 7.0 %) and neutropenia (10.0 % vs. 5.0 %), was manageable across both groups., Conclusion: Anlotinib plus docetaxel offers a viable therapeutic alternative for patients with advanced NSCLC who failed first-line platinum-based treatments., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objective: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were significant and succinct indicators of systemic inflammation. We assessed the influence of stereotactic body radiotherapy (SBRT) on NLR and PLR in patients with locally advanced non-small cell lung cancer (LA-NSCLC)., Methods: We reviewed the medical data of patients with LA-NSCLC who underwent SBRT between 1 January 2013 and 31 December 2018. NLR and PLR values recorded at pre- and post-SBRT were examined. We assessed the correlation between pre/post-SBRT NLR and PLR and survival outcomes. The decision tree evaluation was conducted using Chi-square automatic detection., Results: In total, 213 patients were included in the study with a median follow-up duration of 40.00 (ranging from 5.28 to 100.70) months. Upon dichotomization by a median, we identified that post-SBRT NLR > 5.5 and post-SBRT PLR > 382.0 were negatively associated with shorter overall survival (OS). In the multivariate assessment, post-SBRT PLR > 382.0 was the only factor. Based on post-SBRT PLR, tumor locations, and tumor stage, we categorized patients into low, medium, or high-risk groups., Conclusions: Post-SBRT PLR > 382.0 correlated with survival in patients undergoing SBRT. The decision tree model might play a role in future risk stratification to guide the clinical practice of individualized SBRT for LA-NSCLC., (© 2024 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Non-small cell lung cancer (NSCLC) stands prominent among the prevailing and formidable oncological entities. The immune and metabolic-related molecule Phospholipase A2, group IID (PLA2G2D) exerts promotional effects on tumor progression. However, its involvement in cancer angiogenesis remains elusive. Therefore, this investigation delved into the functional significance of PLA2G2D concerning angiogenesis in NSCLC. This study analyzed the expression and enriched pathways of PLA2G2D in NSCLC tissues through bioinformatics analysis, and measured the expression of PLA2G2D in NSCLC cells using qRT-PCR and western blot (WB). Subsequently, the viability and angiogenic potential of NSCLC cells were assessed employing CCK-8 and angiogenesis assays, respectively. The expression profile of angiogenic factors was analyzed through WB. Finally, the expression of glycolysis pathway-related genes, extracellular acidification rate and oxygen consumption rate, and the levels of pyruvate, lactate, citrate, and malate were analyzed in NSCLC cells using qRT-PCR, Seahorse XF 96, and related kits. Bioinformatics analysis revealed the upregulation of PLA2G2D in NSCLC tissues and its association with VEGF and glycolysis signaling pathways. Molecular and cellular experiments demonstrated that upregulated PLA2G2D promoted the viability, angiogenic ability, and glycolysis pathway of NSCLC cells. Rescue assays revealed that the effects of high expression of PLA2G2D on the viability, angiogenic ability, and glycolysis of NSCLC cells were weakened after the addition of the glycolysis inhibitor 2-DG. In summary, PLA2G2D plays a key role in NSCLC angiogenesis through aerobic glycolysis, displaying great potential as a target for anti-angiogenesis therapy.