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Despite improvements in treatment in recent years, patients with lung adenocarcinoma (LUAD) still face poor prognoses. In this study, we elucidated the potential role of NOP58 ribonucleoprotein in pan-cancer and validated its oncogenic significance in LUAD using bioinformatics and in vitro and in vivo functional assays. NOP58 was found to be overexpressed in various types of tumors. It had great precision for predicting 20 distinct cancer types using receiver operating characteristic curve (ROC) as well as significant connections with the prognoses in particular cancers. In LUAD, NOP58 expression was correlated substantially with the TNM stage, pathologic stage, smoking status, and effectiveness endpoints, when we analyzed its association with clinical characteristics in LUAD. Elevated NOP58 expression was shown as connected with Th2 cell infiltration while also negatively linked with infiltrating other immune cells, such as CD8 T, cytotoxic, and Th1. By inhibiting NOP58 within the LUAD cells, we found a decrease in cells' capability to proliferate, migrate, and invade. Knockdown of NOP58 inhibited tumor growth in mouse xenograft models. Furthermore, the tissue microarray study indicated that there was a greater expression of NOP58 in the tumor tissues compared to adjacent normal tissues in LUAD. Our findings revealed that NOP58 could be an outstanding bio-index for pan-cancer diagnosis and prognosis and an independent prognostic risk factor in LUAD., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

One of the precursors of lung cancer is the presence of lung nodules, and accurate identification of their benign or malignant nature is important for the long-term survival of patients. With the development of artificial intelligence, deep learning has become the main method for lung nodule classification. However, successful deep learning models usually require large number of parameters and carefully annotated data. In the field of medical images, the availability of such data is usually limited, which makes deep networks often perform poorly on new test data. In addition, the model based on the linear stacked single branch structure hinders the extraction of multi-scale features and reduces the classification performance. In this paper, to address this problem, we propose a lightweight interleaved fusion integration network with multi-scale feature learning modules, called MIFNet. The MIFNet consists of a series of MIF blocks that efficiently combine multiple convolutional layers containing 1 × 1 and 3 × 3 convolutional kernels with shortcut links to extract multiscale features at different levels and preserving them throughout the block. The model has only 0.7 M parameters and requires low computational cost and memory space compared to many ImageNet pretrained CNN architectures. The proposed MIFNet conducted exhaustive experiments on the reconstructed LUNA16 dataset, achieving impressive results with 94.82% accuracy, 97.34% F1 value, 96.74% precision, 97.10% sensitivity, and 84.75% specificity. The results show that our proposed deep integrated network achieves higher performance than pre-trained deep networks and state-of-the-art methods. This provides an objective and efficient auxiliary method for accurately classifying the type of lung nodule in medical images., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Recently discovered epigenetic modification lysine lactylation contributes to tumor development and progression in several types of cancer. In addition to the tumor-intrinsic effects, histone lactylation may mediate tumor microenvironment remodeling and immune evasion. In this study, we observed elevated pan-lysine lactylation and histone H3 lysine 18 lactylation (H3K18la) levels in non-small cell lung cancer (NSCLC) tissues, which was positively correlated with poor patient prognosis. Interruption of glycolysis by 2-deoxy-D-glucose and oxamate treatment and silencing of lactate dehydrogenase A and lactate dehydrogenase B reduced H3K18la levels and circumvented immune evasion of NSCLC cells by enhancing CD8+ T-cell cytotoxicity. Mechanistically, H3K18la directly activated the transcription of pore membrane protein 121 (POM121), which enhanced MYC nuclear transport and direct binding to the CD274 promoter to induce PD-L1 expression. In a mouse NSCLC xenograft model, combination therapy with a glycolysis inhibitor and an anti-PD-1 antibody induced intratumoral CD8+ T-cell function and exhibited strong antitumor efficacy. Overall, this work revealed that H3K18la potentiates the immune escape of NSCLC cells by activating the POM121/MYC/PD-L1 pathway, which offers insights into the role of posttranslational modifications in carcinogenesis and provides a rationale for developing an epigenetic-targeted strategy for treating NSCLC. Significance: H3K18 lactylation supports immunosuppression in non-small cell lung cancer by inducing POM121 to increase MYC activity and PD-L1 expression, which can be reversed by metabolic reprogramming and immunotherapy treatment., (©2024 American Association for Cancer Research.)

Aim: Due to the rarity of lung cancer with cystic imaging manifestations, we explore the clinical features and survival prognosis of such tumors., Materials and Methods: Imaging characteristics were used to categorize 3,556 patients who underwent surgery for isolated primary lung cancer into one of three groups: those with cystic lung cancer (149), solid lung cancer (1,399), and ground-glass lung cancer (1,160). Propensity score matching by sex and age was performed to analyze the differences in clinical characteristics of lung cancer among the three groups and the correlation between clinical characteristics of cystic lesions and progression-free survival (PFS)., Results: The three groups of patients differed in various aspects, including pathological type, smoking history, tumor stage, type of surgery, histological grading, and PFS (P < 0.05). The results of the multifactorial analysis indicated that lung cancer type, pathological type, lymph node metastasis, tumor stage, and histologic grading were independent prognostic factors for lung cancer (P < 0.05). After comparison, there was a difference in prognosis between cystic lung cancer and ground-glass lung cancer (P < 0.05)., Conclusion: The clinical features of cystic lung cancer are significantly different from those of ground-glass lung cancer and solid lung cancer. Cystic lesions are independent influencing factors affecting lung cancer, and the prognosis of cystic lung cancer is worse than that of ground-glass lung cancer., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Despite breakthroughs of immunotherapy synergistically combined with blockade of vascular endothelial growth factor receptor, several patients with advanced non-small cell lung cancer (NSCLC) experience non-response or followed relapse. Organized lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are found to be associated with improved response to immunotherapy. Here, we explore the landscapes of TLSs in tumour tissues from a real-world retrospective study. Our investigation showed that with a median follow-up of 11.2 months, the ORR was 28.6% (18/63, 95% CI 17.9-41.3) and the median PFS was 6.1 (95% CI 5.5-6.6) months in NSCLC patients treated with PD-1 blockade combined with anlotinib. By multiplex immunofluorescence (mIF) analysis, spatially, more TLSs and high CD20+ B-cell ratio in TLSs were associated with higher ORR. High density of intratumoral CD8+ T cells showed better ORR and PFS. The numbers of CD8+ T cells with a distance within 20 μm and 20-50 μm between tumour cells were higher in responders than non-responders. But responders had significantly higher TLSs within 20 μm rather than within 20-50 μm of tumour cells than non-responders. The inflamed immunophenotyping occupied higher proportions in responders and was associated with better PFS. Besides, tumour cells in non-responders were found more temporal cell-in-cell structures than responders, which could protect inner cells from T-cell attacks. Taken together, landscape of TLSs and proximity architecture may imply superior responses to PD-1 blockade combined with anlotinib for patients with advanced non-small cell lung cancer., (© 2024 John Wiley & Sons Ltd.)

Comprehensive N6-methyladenosine (m6A) epitranscriptomic profiling of primary tumors remains largely uncharted. Here, we profiled the m6A epitranscriptome of 10 nonneoplastic lung tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating the corresponding transcriptomic, proteomic, and extensive clinical annotations. We identified distinct clusters and genes that were exclusively linked to disease progression through m6A modifications. In comparison with nonneoplastic lung tissues, we identified 430 transcripts to be hypo-methylated and 222 to be hyper-methylated in tumors. Among these genes, EML4 emerged as a novel metastatic driver, displaying significant hypermethylation in tumors. m6A modification promoted the translation of EML4, leading to its widespread overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics by interacting with ARPC1A, enhancing lamellipodia formation, cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. METTL3 small-molecule inhibitor markedly diminished both EML4 m6A and protein abundance and efficiently suppressed lung metastases in vivo. Significance: Our study reveals a dynamic and functional epitranscriptomic landscape in LUAD, offering a valuable resource for further research in the field. We identified EML4 hypermethylation as a key driver of tumor metastasis, highlighting a novel therapeutic strategy of targeting EML4 to prevent LUAD metastasis., (©2024 The Authors; Published by the American Association for Cancer Research.)

Recent studies confirm the critical roles of endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) in malignant behavior of various cancers. Nevertheless, what function ERO1L plays in lung adenocarcinoma (LUAD) remains uncovered. The expressions and clinical significance of ERO1L in LUAD were investigated using the TCGA dataset. The ERO1L levels were examined by RT-qPCR. The LUAD cell proliferation was valued using colony formation as well as CCK-8 assays. The invasion and migration abilities of LUAD cells were detected through Transwell in addition to wound healing assays. The effects of ERO1L on LUAD cell apoptosis were determined by flow cytometric analysis. Moreover, we also established mouse xenograft models of LUAD cells to confirm the functions of ERO1L in vivo. The ERO1L levels in tumors were identified by immunohistochemistry. Western blot was used for the detection of the levels of Wnt/βcatenin signaling-related proteins. The TCGA database revealed that ERO1L expressions were higher in LUAD tissues than those in non-cancerous tissues. ERO1L overexpression was related to poorer overall survival of LUAD patients. In addition, ERO1L silence suppresses LUAD cell clone formation, proliferation, migration as well as invasion but induces apoptosis. Moreover, we also verified that ERO1L silence could promote LUAD growth in vivo. Based on the mechanism analysis, ERO1L was confirmed to regulate LUAD development via Wnt/βcatenin cascade signal. ERO1L, the expression of which was increased in LUAD tissues, functioned as an oncogene. ERO1L silence significantly attenuated LUAD tumorigenesis, likely via inhibition of Wnt/βcatenin signaling, indicating that ERO1L could be exploited as a promising biomarker in LUAD treatment.

The implementation of chemoradiation combinations has gained great momentum in clinical practices. However, the full utility of this paradigm is often restricted by the discordant tempos of action of chemotherapy and radiotherapy. Here, a gold nanoparticle-based radiation-responsive nanovesicle system loaded with cisplatin and veliparib, denoted as CV-Au NVs, is developed to augment the concurrent chemoradiation effect in a spatiotemporally controllable manner of drug release. Upon irradiation, the in situ generation of •OH induces the oxidation of polyphenylene sulfide from being hydrophobic to hydrophilic, resulting in the disintegration of the nanovesicles and the rapid release of the entrapped cisplatin and veliparib (the poly ADP-ribose polymerase (PARP) inhibitor). Cisplatin-induced DNA damage and the impairment of the DNA repair mechanism mediated by veliparib synergistically elicit potent pro-apoptotic effects. In vivo studies suggest that one-dose injection of the CV-Au NVs and one-time X-ray irradiation paradigm effectively inhibit tumor growth in the A549 lung cancer model. This study provides new insight into designing nanomedicine platforms in chemoradiation therapy from a vantage point of synergizing both chemotherapy and radiation therapy in a spatiotemporally concurrent manner., (© 2024 Wiley‐VCH GmbH.)

Objective: To investigate the effect of Euphorbia helioscopia on biological behaviors of non-small cell lung cancer (NSCLC) cells., Methods: NSCLC cell lines PC-9 and A549 treated with different concentrations of Euphorbia helioscopia preparations were examined for changes in proliferation, apoptosis, invasion and migration using CCK-8 assay, colony formation assay, flow cytometry, wound healing assay and Transwell assay. Western blotting was performed to detect the changes in protein expressions of Bax, Bcl-2, E-cadherin, vimentin, MMP2, and MMP9 in the treated cells. PC-9 cells were injected subcutaneously into BALB/C nude mice to establish a nude mouse subcutaneous tumor model. According to the growth of subcutaneous tumors, mice were randomly divided into control group: gavaged daily with saline; Euphorbia helioscopia -treated group: gavaged daily with Euphorbia helioscopia 65 mg/mL, and Euphorbia helioscopia granules were dissolved in saline; cisplatin-treated group: injected intraperitoneally with cisplatin 4 mg/kg every 5 days, 6 mice per group. The subcutaneous tumor volume and mass changes of mice were measured, and the toxic effects of Euphorbia helioscopia on heart, liver, spleen, lung and kidney as well as the therapeutic effects of Euphorbia helioscopia were observed in the mice bearing tumor., Results: Euphorbia helioscopia granules concentration-dependently inhibited the proliferation and survival of PC-9 and A549 cells, significantly promoted cell apoptosis, suppressed invasion and migration abilities of the cells, up-regulated the expression levels of E-cadherin and Bax, and down-regulated the expressions of Bcl-2, vimentin, MMP2, and MMP9. In the tumor-bearing mice, treatment with Euphorbia helioscopia significantly inhibited tumor growth without producing obvious toxicity in the vital organs., Conclusion: Euphorbia helioscopia can inhibit proliferation, invasion, and migration and induces apoptosis of NSCLC cells in vitro .

Objective: To investigate the regulatory effects of LINC00467 on proliferation and metastasis of lung adenocarcinoma cells and the involvement of autophagy in its regulatory mechanism., Methods: LINC00467 expression levels in lung adenocarcinoma tissues and their correlation with the patients' survival outcomes were analyzed using data from TCGA database. LINC00467 expression was also examined using qRT-PCR in human bronchial epithelial cells 16HBE and lung adenocarcinoma cell lines A549 and H1299. In A549 and H1299 cells transfected with a short hairpin RNA targeting LINC00467 (shLINC00467), the effects of 3-methyladenine (3-MA, an autophagy inhibitor) and BML-275 (an AMPK inhibitor) treatment on cell proliferation, migration, and expressions of LC3 and the AMPK/mTOR pathway proteins were tested using colony formation assay, wound-healing and Transwell assays, immunofluorescence staining and Western blotting. GSEA enrichment analysis was conducted to analyze the correlation between LINC00467 and the autophagy pathway., Results: The expression level of LINC00467 was significantly higher in lung adenocarcinoma tissues than in the adjacent tissues ( P < 0.001) and increased progressively with the clinical stage ( P < 0.05), and its high expression was associated with a poor overall survival ( P = 0.049) and a high first progression rate ( P =0.026) of the patients. LINC00467 expression was also significantly higher in A549 and H1299 cells than in 16HBE cells. In A549 and H1299 cells, LINC00467 knockdown significantly decreased colony-forming, migration and invasion abilities of the cells, lowered p-mTOR/mTOR and p62 expressions, and increased p-AMPK/AMPK expressions and LC3Ⅱ/Ⅰ ratio, and these effects were strongly attenuated by application of either 3-MA or BML-275. GSEA analysis suggested an inhibitory effect on LINC00467 on the autophagy pathway (|NES| > 1, P < 0.05, FDR < 0.25)., Conclusion: High expressions of LINC00467 promote proliferation and metastasis of lung adenocarcinoma cells possibly by inhibiting cell autophagy mediated by the AMPK/mTOR signaling pathway.

Lung adenocarcinoma (LUAD) is a study that examines the prognostic value of lactate metabolism genes in tumor cells, which are associated with clinical prognosis. We analyzed the expression and clinical data for LUAD from The Cancer Genome Atlas database, using the GSE68465 dataset from the Gene Expression Omnibus and the MSigDB database. LASSO Cox regression and stepwise Cox regression were used to identify the optimal lactate metabolism gene signature. Differences in immune infiltration, tumor mutation burden (TMB), and response to immune checkpoint blockade (ICB) therapy were evaluated between groups. LASSO and Cox regression analyses showed an eight-lactate metabolism gene signature for model construction in both TCGA cohort and GSE68465 data, with higher survival outcomes in high-risk groups. The lactate metabolism risk score had an independent prognostic value (hazard ratio: 2.279 [1.652-3.146], P < .001). Immune cell infiltration differed between the risk groups, such as CD8+ T cells, macrophages, dendritic cells, mast cells, and neutrophils. The high-risk group had higher tumor purity, lower immune and stromal scores, and higher TMB. High-risk samples had high tumor immune dysfunction and exclusion (TIDE) scores and low cytolytic activity (CYT) scores, indicating a poor response to ICB therapy. Similarly, most immune checkpoint molecules, immune inhibitors/stimulators, and major histocompatibility complex (MHC) molecules were highly expressed in the high-risk group. The 8-lactate metabolism gene-based prognostic model predicts patient survival, immune infiltration, and ICB response in patients with LUAD, driving the development of therapeutic strategies to target lactate metabolism., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Lung cancer accounts for the highest cancer-related mortality worldwide. While immunotherapies targeting anti-tumor immune responses have demonstrated efficacy in clinical practice, the demand for novel treatment modalities remains urgent. Oncolytic viruses (OVs), which selectively kill tumor cells while stimulating an anti-tumor immune response, represent a potential breakthrough in lung cancer therapy. The induction of anti-tumor immunity by OVs is central to their overall therapeutic effectiveness. Many natural receptors on the surface of cancer cells are dysregulated, providing potential entry points for OVs. Furthermore, the inherent dysregulation of some key signaling pathways in lung cancer cells promotes proliferation, progression and metastasis, which may facilitate selective viral replication. In this review, we explore the application of OVs in lung cancer by analyzing several major OVs and their corresponding entry receptors. Then, we also examine the key signaling pathways and molecules with the potential to synergize with OVs in modulating the immune tumor microenvironment. Finally, we discuss the combination and administration strategies that warrant further clinical trials for validation. Despite certain limitations, the tolerability of OVs positions virotherapy as a promising avenue in the future of lung cancer treatment., 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 Dong, Luo, He, Zhang, Zeng and Chen.)

Objectives: The goal was to explore clinical factors and build a predictive model for the disease-free and overall survival of patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant chemotherapy combined with immune checkpoint inhibitors., Methods: Inclusion criteria for patients in this multicentre study were as follows: (i) Patients who were diagnosed with stages I-III NSCLC after a bronchoscopy biopsy or puncture; (ii) patients who were examined with computed tomography/positron emission tomography-computed tomography before treatment and surgery; (iii) patients who received neoadjuvant chemotherapy combined with immune checkpoint inhibitors for 2 to 6 cycles preoperatively; (iv) patients whose peripheral blood indicators and tumour markers were assessed before treatment and preoperatively; (v) patients who underwent radical lung cancer surgery after neoadjuvant therapy. Cases were divided into high- and low-risk groups according to 78 clinical indicators based on a 10-fold Least Absolute Shrinkage and Selection Operator selection. We used Cox proportional hazards models to predict disease-free and overall survival. Then, we used time-dependent area under the curve and decision curve analyses to examine the accuracy of the results., Results: Data were collected continuously, and 212 and 85 cases were randomly assigned to training and testing sets, respectively. The area under the curve for the prediction of disease-free survival (training: 1 year, 0.83; 2 years, 0.81; 3 years, 0.83 versus testing: 1 year, 0.65; 2 years, 0.66; 3 years, 0.70), overall survival (training: 1 year, 0.86; 2 years, 0.85; 3 years, 0.86 versus testing: 1 year, 0.66; 2 years, 0.57; 3 years, 0.70) were determined. The coefficient factors including pathological response; preoperative tumour maximum diameter; preoperative lymph shorter diameter; preoperative tumour and lymph maximum standardized uptake value; change in tumour standardized uptake value preoperatively; and blood-related risk factors were favourably associated with prognosis (P < 0.001)., Conclusions: Our prediction model, which integrated data from preoperative positron emission tomography-CT, preoperative blood parameters and pathological response, was able to make highly accurate predictions for disease-free and overall survival in patients with NSCLC receiving neoadjuvant immunity with chemical therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Scope: The association between a planetary and sustainable EAT-Lancet diet and lung cancer remains inconclusive, with limited exploration of the role of genetic susceptibility and inflammation., Methods and Results: The study includes 175 214 cancer-free participants in the UK Biobank. Fourteen food components are collected from a 24-h dietary recall questionnaire. A polygenic risk score is constructed through capturing the overall risk variants for lung cancer. Sixteen inflammatory biomarkers are assayed in blood samples. Participants with the highest EAT-Lancet diet scores (≥12) have a lower risk of lung cancer incidence (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.51-0.80) and mortality (HR = 0.65, 95% CI: 0.48-0.88), compared to those with the lowest EAT-Lancet diet scores (≤8). Interestingly, there is a significantly protective trend against both lung adenocarcinoma and lung squamous cell carcinoma with higher EAT-Lancet diet scores. Despite no significant interactions, a risk reduction trend for lung cancer is observed with increasing EAT-Lancet diet scores and decreasing genetic risk. Ten inflammatory biomarkers partially mediate the association between the EAT-Lancet diet and lung cancer risk., Conclusion: The study depicts a lower risk of lung cancer conferred by the EAT-Lancet diet associated with lower inflammation levels among individuals with diverse genetic predispositions., (© 2024 Wiley‐VCH GmbH.)

Background: The hypothesized link between low-density lipoprotein (LDL) and oncogenesis has garnered significant interest, yet its explicit impact on lung adenocarcinoma (LUAD) remains to be elucidated. This investigation aims to demystify the function of LDL-related genes (LRGs) within LUAD, endeavoring to shed light on the complex interplay between LDL and carcinogenesis., Methods: Leveraging single-cell transcriptomics, we examined the role of LRGs within the tumor microenvironment (TME). The expression patterns of LRGs across diverse cellular phenotypes were delineated using an array of computational methodologies, including AUCell, UCell, singscore, ssGSEA, and AddModuleScore. CellChat facilitated the exploration of distinct cellular interactions within LDL&#95;low and LDL&#95;high groups. The findmarker utility, coupled with Pearson correlation analysis, facilitated the identification of pivotal genes correlated with LDL indices. An integrative approach to transcriptomic data analysis was adopted, utilizing a machine learning framework to devise an LDL-associated signature (LAS). This enabled the delineation of genomic disparities, pathway enrichments, immune cell dynamics, and pharmacological sensitivities between LAS stratifications., Results: Enhanced cellular crosstalk was observed in the LDL&#95;high group, with the CoxBoost+Ridge algorithm achieving the apex c-index for LAS formulation. Benchmarking against 144 extant LUAD models underscored the superior prognostic acuity of LAS. Elevated LAS indices were synonymous with adverse outcomes, diminished immune surveillance, and an upsurge in pathways conducive to neoplastic proliferation. Notably, a pronounced susceptibility to paclitaxel and gemcitabine was discerned within the high-LAS cohort, delineating prospective therapeutic corridors., Conclusion: This study elucidates the significance of LRGs within the TME and introduces an LAS for prognostication in LUAD patients. Our findings accentuate putative therapeutic targets and elucidate the clinical ramifications of LAS deployment., (© 2024 Wiley Periodicals LLC.)

Purpose: To construct a nomogram for predicting lymphovascular invasion (LVI) in N0 stage non-small cell lung cancer (NSCLC) using dual-energy computed tomography (DECT) findings combined with clinical findings., Methods: We retrospectively recruited 135 patients with N0 stage NSCLC from two hospitals underwent DECT before surgery and were divided into development cohort (n = 107) and validation cohort (n = 28). The clinical findings (baseline characteristics, biochemical markers, serum tumor markers and Immunohistochemical markers), DECT-derived parameters (iodine concentration [IC], effective atomic number [Eff-Z] and normalized iodine concentration [NIC], iodine enhancement [IE] and NIC ratio [NICr]) and Fractal dimension (FD) were collected and measured. A nomogram was constructed using significant findings to predict LVI in N0 stage NSCLC and was externally validated., Results: Multivariable analysis revealed that lymphocyte count (LYMPH, odds ratio [OR]: 3.71, P=0.014), IC in arterial phase (ICa, OR: 1.25, P=0.021), NIC in venous phase (NICv, OR: 587.12, P=0.009) and FD (OR: 0.01, P=0.033) were independent significant factors for predicting LVI in N0 stage NSCLC, and were used to construct a nomogram. The nomogram exhibited robust predictive capabilities in both the development and validation cohort, with AUCs of 0.819 (95 % CI: 72.6-90.4) and 0.844 (95 % CI: 68.2-95.8), respectively. The calibration plots showed excellent agreement between the predicted probabilities and the actual rates of positive LVI, on external validation., Conclusions: Combination of clinical and DECT imaging findings could aid in predicting LVI in N0 stage NSCLC using significant findings of LYMPH, ICa, NICv and FD., 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.)

Background: For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC., Methods: This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18-70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0-42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003., Findings: From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58-68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33-56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2-62·0]) than in the 45 Gy group (39·5 months [27·5-51·4]; hazard ratio 0·55 [95% CI 0·37-0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3-4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit., Interpretation: Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18-70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option., Funding: Chinese Society of Clinical Oncology-Linghang Cancer Research, the Wu Jieping Medical Foundation, and Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital and Beijing Municipal Administration of Hospitals Incubating Program., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: The standard treatment schedule for unresectable stage III non-small cell lung cancer (NSCLC) is chemotherapy with concurrent radiation therapy (60 Gy delivered in 30 fractions), although moderately hypofractionated radiation therapy (Hypo-RT) has also been considered as an alternative strategy. This study aimed to compare the efficacy and toxicity of moderately Hypo-RT with helical TomoTherapy versus conventionally fractionated radiation therapy (Con-RT) in patients with unresectable stage III NSCLC receiving concurrent chemotherapy., Methods and Materials: In this randomized, multicenter, nonblinded phase 3 clinical trial, eligible patients were randomised at a 1:1 ratio to either the Hypo-RT group (60 Gy in 20 fractions) or Con-RT group (60 Gy in 30 fractions). All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) in the intention-to-treat population. The secondary endpoints were progression-free survival and treatment-related adverse events., Results: A total of 146 patients were enrolled from July 27, 2018, to November 1, 2021. The median follow-up was 46 months. The 3-year OS rates in the Hypo-RT and Con-RT groups were 58.4% and 38.4%, respectively (P = .02). The median OS from randomisation was 41 months in the Hypo-RT group and 30 months in the Con-RT group (hazard ratio, 0.61; 95% confidence interval, 0.40-0.94; P = .02). There was no significant difference in the rates of grade ≥2 treatment-related adverse events between the 2 groups., Conclusions: Moderately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC, while maintaining toxicity rates., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted cancer services worldwide. We examined the effect of the first three pandemic waves on the number of electronic (e)-referrals to rapid access clinics (RACs) for breast, lung and prostate cancer in Ireland., Methods: This study used a retrospective, repeated cross-sectional design. The predicted weekly number of e-referrals by suspected cancer types from March 2020 to May 2021 was calculated using the Holt-Winters seasonal smoothing method, based on the observed numbers from a representative pre-pandemic period (01 January 2019 to 01 March 2020) and compared this with the observed number across the first three pandemic waves (02 March 2020 to 09 May 2021). Percentage differences were calculated between observed and predicted numbers of e-referrals for the three RACs and patterns were examined in each wave., Results: Observed e-referrals were lower than predicted for all three RACs in the first wave of the pandemic (15.7% lower for breast, 39.5% lower for lung and 28.1% lower for prostate) with varying levels of recovery in the second and third waves for the three e-referral types., Conclusions: The COVID-19 pandemic impacted patterns of e-referrals to RACs in the first three pandemic waves in Ireland. Early identification of changes in engagement with health services, such as a decrease in primary care presentations with a resultant decrease in e-referrals to RACs can allow for a rapid response from cancer control programmes. Continued surveillance of the impact of service disruption on cancer services allows policy makers and strategic leaders in cancer control programmes to respond rapidly to mitigate the impact on cancer outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8 + T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics., (© 2024. The Author(s).)

Objectives: Low-dose computed tomography (LDCT) has emerged as a pivotal tool for detecting lung cancer among ever-smokers. This study aims to evaluate the gender-specific outcomes of LDCT screening within the Chinese never-smoking population., Methods: We conducted a single-center, retrospective cohort study, which analyzed LDCT screening outcomes for 42,018 asymptomatic participants. Specifically, we focused on assessing gender-specific differences in the prevalence of pulmonary nodules, and the incidence of lung cancer diagnosis among never-smokers., Results: Among the 42,018 eligible participants, 41.50% were females and 58.50% were males. Most participants were non-smokers (77.57%), with a significantly higher proportion of non-smokers among females than males (99.33% vs. 62.14%). Pulmonary nodules were identified in 2.66% of participants, with a higher prevalence in females (2.99%) than males (2.43%) (p < 0.001). Non-smoking females had a higher incidence of positive nodules than non-smoking males (2.98% vs. 2.38%, p < 0.001). Invasive biopsies were performed in 334 individuals with nodules, confirming lung cancer in 258 cases. The majority of these cancer cases were non-smokers (212), with non-smoking females showing a higher incidence (0.85%) compared to males (0.43%) (p < 0.001). There was no significant difference in the false-positive rates between non-smoking females (0.14%) and males (0.13%). Multivariate analysis showed that never-smoking women were more likely to undergo biopsies (OR 1.65, p = 0.0016) and had a higher, though not statistically significant, probability of lung cancer diagnosis (OR 1.84, p = 0.06)., Conclusion: This study elucidates sex-based differences within the Chinese population, revealing a higher prevalence of pulmonary nodules and lung cancers among non-smoking females. These findings offer valuable reference for both clinical practice and future research initiatives., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To evaluate the value of computed tomography (CT)-based radiomics combined with clinical-genetic features in predicting brain metastasis in patients with stage III/IV epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC)., Methods: The study included 147 eligible patients treated at our institution between January 2018 and May 2021. Patients were randomly divided into two cohorts for model training (n = 102) and validation (n = 45). Radiomics features were extracted from the chest CT images before treatment, and a radiomics signature was constructed using the Least Absolute Shrinkage and Selection Operator regression. Kaplan-Meier survival analysis was used to describe the differences in brain metastasis-free survival (BM-FS) risk. A clinical-genetic model was developed using Cox regression analysis. Radiomics, genetic, and combined prediction models were constructed, and their predictive performances were evaluated by the concordance index (C-index)., Results: Patients with a low radiomics score had significantly longer BM-FS than those with a high radiomics score in both the training (p < 0.0001) and the validation (p = 0.0016) cohorts. The C-indices of the nomogram, which combined the radiomics signature and N stage, overall stage, third-generation tyrosine kinase inhibitor treatment, and EGFR mutation status, were 0.886 (95% confidence interval [CI] 0.823-0.949) and 0.811 (95% CI 0.719-0.903) in the training and validation cohorts, respectively. The combined model achieved a higher discrimination and clinical utility than the single prediction models., Conclusions: The combined radiomics-genetic model could be used to predict BM-FS in stage III/IV NSCLC patients with EGFR mutations., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Combination drug therapy represents an effective strategy for treating certain drug-resistant and intractable cancer cases. However, determining the optimal combination of drugs and dosages is challenging due to clonal diversity in patients' tumors and the lack of rapid drug sensitivity evaluation methods. Microfluidic technology offers promising solutions to this issue. In this study, we propose a versatile microfluidic chip platform capable of integrating all processes, including dilution, treatment, and detection, for in vitro drug sensitivity assays. This platform innovatively incorporates several modules, including automated discrete drug logarithmic concentration generation, on-chip cell perfusion culture, and parallel drug treatments of cancer cell models. Moreover, it is compatible with microplate readers or high-content imaging systems for swift detection and automated monitoring, simplifying on-chip drug evaluation. Proof of concept is demonstrated by assessing the in vitro potency of two drugs, cisplatin, and etoposide, against the lung adenocarcinoma A549 cell line, under both single-drug and combination treatment conditions. The findings reveal that, compared to conventional microplate approaches with static cultivation, this on-chip automated perfusion bioassays yield comparable IC 50 values with lower variation and a 50 % reduction in drug preparation time. This versatile dilution-treatment-detection microfluidic platform offers a promising tool for rapid and precise drug assessments, facilitating in vitro drug sensitivity evaluation in personalized cancer chemotherapy., 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 (LUAD) is a leading cause of cancer‑related death due to its aggressive nature and metastatic potential. The present study aimed to explore the expression of phospholipid phosphatase 2 (PPAP2C) in LUAD, and its effect on cell migration and invasion, with a particular focus on its association with the ERK/JNK signaling pathway and epithelial‑mesenchymal transition (EMT). The expression of PPAP2C in LUAD was analyzed using data from The Cancer Genome Atlas database. Pearson's correlation coefficient analysis was used to assess the correlation between PPAP2C and genes such as MAPK1, MAPK3, MAPK8, CDH1, CDH2 and SNAI1. Subsequently, the PPAP2C gene was silenced in A549 and H1299 LUAD cell lines using siRNA vectors, followed by assessments of gene expression, cell migration, invasion and protein interaction using reverse transcription‑quantitative PCR, western blotting, wound healing assay, Transwell invasion assay, molecular docking analysis, co‑immunoprecipitation and immunofluorescence staining. The results showed that PPAP2C was significantly upregulated in LUAD tissues compared with that in normal tissues. In addition, high levels of PPAP2C were significantly correlated with MAPK3, MAPK8, CDH1 and SNAI1. Notably, PPAP2C silencing significantly inhibited cell migration and invasion. Additionally, it reduced the phosphorylation levels of ERK and JNK proteins. PPAP2C showed specific binding sites with ERK1, and co‑precipitated with ERK1 in both A549 and H1299 cells. Furthermore, PPAP2C silencing decreased the expression levels of N‑cadherin and Snail, while increasing E‑cadherin expression, thereby inhibiting EMT. In conclusion, PPAP2C may be highly expressed in LUAD tissues, and could promote cell migration and invasion by activating the ERK/JNK signaling pathway and inducing EMT. These findings provide a novel potential target for the diagnosis and treatment of LUAD.

Despite being the leading cause of lung cancer-related deaths, the underlying molecular mechanisms driving metastasis progression are still not fully understood. Transfer RNA-derived fragments (tRFs) have been implicated in various biological processes in cancer. However, the role of tRFs in lung adenocarcinoma (LUAD) remains unclear. Our study identified a tRF, tRF-Val-CAC-024, associated with the high-risk component of LUAD, through validation using 3 cohorts. Our findings demonstrated that tRF-Val-CAC-024 acts as an oncogene in LUAD. Mechanistically, tRF-Val-CAC-024 was revealed to bind to aldolase A (ALDOA) dependent on Q125/E224 and promote the oligomerization of ALDOA, resulting in increased enzyme activity and enhanced aerobic glycolysis in LUAD cells. Additionally, we provide preliminary evidence of its potential clinical value by investigating the therapeutic effects of tRF-Val-CAC-024 antagomir-loaded lipid nanoparticles (LNPs) in cell-line-derived xenograft models. These results could enhance our understanding of the regulatory mechanisms of tRFs in LUAD and provide a potential therapeutic target., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to delineate the clinical presentations, imaging features, pathological characteristics, therapeutic strategies, and outcomes of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma, thereby deducing the most efficacious treatment paradigm., Methods: We conducted a retrospective review of 14 patients diagnosed with pulmonary MALT lymphoma at the Second Xiangya Hospital, affiliated with Central South University, between September 2007 and September 2022, focusing on their clinical profiles, diagnostic pathways, treatment modalities, and prognostic outcomes., Results: The cohort's median age was 60 years (ranging from 44 to 81 years), with 64.29% being female and only 14.29% having a history of smoking. The incidence of immunodeficiency diseases among the patients was notably low. Imaging typically revealed pulmonary nodules and masses, with air bronchogram signs evident in 9 patients and pleural effusion in 2. CD20 expression was markedly positive across the board in all patients with pulmonary MALT lymphoma. Among the 12 patients who received intervention, 6 were treated with chemotherapy alone, 2 underwent surgical resection, and 4 benefitted from a combined approach of chemotherapy and surgery. Over the monitoring period, 2 patients succumbed to their disease. The estimated 5- and 10-year overall survival (OS) rates were 91.67% and 76.39%, respectively, with the median progression-free survival (PFS) reaching 7 years. Comparative analysis revealed no significant disparity in PFS between patients treated exclusively with chemotherapy and those receiving both chemotherapy and surgical intervention (P = 0.22)., Conclusion: Pulmonary MALT lymphoma typically exhibits a slow course, with gradual progression and a predominantly positive prognosis. Chemotherapy emerges as the preferred therapeutic option for managing this malignancy., (© 2024. The Author(s).)

Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is rare and is associated with poor prognosis. However, the standard treatment protocols for patients with SCLC transformation remain unknown. Here, we report the case of a patient with advanced EGFR exon 19 deletion (19del) NSCLC who underwent SCLC transformation during targeted therapy. Biopsies and genetic testing were performed to adjust treatment regimens accordingly. The patient responded favorably to a combined treatment regimen comprising etoposide plus cisplatin chemotherapy and adebrelimab plus osimertinib. This case highlights the critical importance of acknowledging tumor heterogeneity in clinical decision-making and identifying potentially effective treatment options for patients with SCLC transformation. Additionally, we reviewed cases of the transformation of NSCLC to SCLC from 2017 to 2023., 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 Li, Luan, Zhang, Wang, Guo, Lv, Qiu and Zhao.)

Background: Isoliquiritigenin (ISL) is an important pharmacological constituent of Glycyrrhiza glabra, which possesses a range of physiological and pharmacological activities, as well as significant antitumor activity, and can be used as a potential drug for targeted cancer therapy. LINC01503 is an oncogene, which has been closely associated with the malignant biological processes of many cancers. The aim of this study was to investigate the effects of ISL on the proliferation, apoptosis, invasion and migration of lung squamous carcinoma cells by regulating LINC01503., Methods: Plasma was collected from lung squamous carcinoma patients and healthy individuals treated at Tangshan People's Hospital from January 2021 to December 2022. The expression of LINC01503 in lung squamous carcinoma plasma, tissues and cells was detected by real-time quantitative fluorescence polymerase chain reaction (qRT-PCR). Lung squamous carcinoma cells were treated with different concentrations of ISL for 24 h, and LINC01503 expression was detected by qRT-PCR. The cells were treated in groups: si-NC group, si-LINC01503 group, DMSO (0.1% dimethyl sulfone) group, ISL group, pc DNA3.1(+)-NC group, pc DNA3.1(+)-LINC01503 group, ISL+pc DNA3.1(+)-NC group and ISL+pc DNA3.1(+)- LINC01503 groups. CCK-8 assay, clone formation assay, flow cytometry, Transwell assay and scratch assay were used to explore the effect of LINC01503 on the functional phenotype of lung squamous carcinoma cells., Results: Fluorescence in situ hybridization results showed that the average fluorescence intensity of LINC01503 in tissue microarrays of lung squamous carcinoma patients was higher than that in paracancerous tissues (P<0.05). The expression of LINC01503 in the plasma of patients with lung squamous carcinoma was higher than that in the plasma of healthy individuals (P<0.05). Knockdown of LINC01503 inhibited the proliferation, invasion and migration of lung squamous carcinoma cells and promoted apoptosis (P<0.05). ISL inhibited the proliferation, invasion, migration and promoted apoptosis of lung squamous carcinoma cells (P<0.05). Overexpression of LINC01503 followed by intervention with ISL reversed the promotional effect of overexpression of LINC01503 on the proliferation, invasion and migration of lung squamous carcinoma cells as well as the inhibitory effect on apoptosis (P<0.05)., Conclusions: LINC01503 was highly expressed in lung squamous carcinoma, and LINC01503 could promote the proliferation, invasion and migration of lung squamous carcinoma cells and inhibit the apoptosis, ISL could inhibit the proliferation, invasion and migration of lung squamous carcinoma cells and promote apoptosis of lung squamous carcinoma cells by regulating the expression of LINC01503.

Background: Lung cancer is a significant health concern, and is often accompanied by comorbid depression, leading to worsened prognosis and decreased quality of life for patients. This study aimed to investigate the potential influence of a diet rich in Omega-3 fatty acids on the quality of life of patients with squamous cell lung cancer and comorbid depression., Methods: A retroactive analysis of clinical information from patients with squamous cell lung cancer and comorbid depression admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from June 2022 to June 2023 was conducted. The patients were classified into two groups on the basis of different dietary care approaches: the Routine Dietary Group and the Omega-3 Fatty Acids Group. Baseline characteristics, pulmonary function tests, dietary intake, depression scoring, and quality of life scores were compared between the two groups., Results: 103 patients in total were included, with 51 in the Routine Dietary Group and 52 in the Omega-3 Fatty Acids Group. The Omega-3 Fatty Acids Group exhibited significantly higher ingestion of Omega-3 fatty acids in comparison with the Routine Dietary Group (3.15 ± 0.64 g/day vs. 2.93 ± 0.28 g/day, p = 0.022). Despite similar baseline pulmonary function tests, patients in the Omega-3 Fatty Acids Group showed significantly higher scores in physical (70.17 ± 4.81 vs. 68.18 ± 5.03, p = 0.043) and emotional (71.29 ± 4.58 vs. 69.38 ± 4.25, p = 0.030) functioning, as well as lower scores in insomnia (27.41 ± 4.51 vs. 29.34 ± 4.21, p = 0.027) and constipation (7.34 ± 1.66 vs. 8.43 ± 3.36, p = 0.040)., Conclusion: The study provided insights into the potential impact of a diet rich in Omega-3 fatty acids on the quality of life of patients with squamous cell lung cancer and complicating depression, suggesting that dietary interventions emphasizing Omega-3 fatty acids may be conducive to improving physical and emotional functioning, as well as symptom management, in this patient population.

Currently, there is no consensus regarding the extent of surgery for stage I pulmonary carcinoid (PC) tumors, which encompass typical carcinoid (TC) and atypical carcinoid (AC) tumors. Sublobar resection includes segmental resection and wedge resection; the former is regarded as a type of anatomical resection that is better suited for tumor treatment. Therefore, it needs to be further verified whether differences exist in the effects of the two surgical methods on the survival time of patients. Propensity score matching (PSM) was used. The primary endpoints were cancer-specific survival (CSS) and overall survival (OS) time. Survival differences were analyzed via the Kaplan-Meier method and the log-rank test. There was no significant difference in survival between the sublobar resection and lobectomy groups after PSM in either the TC or AC tumor groups (all p > 0.05). A total of 1680 patients underwent pulmonary wedge resection (TC: n = 1547, AC: n = 133), and 398 patients underwent segmental resection (TC: n = 365, AC: n = 33). After PSM, there were no statistically significant differences in survival, regardless of whether OS or CSS was considered the primary endpoint (OS: p = 0.337; CSS: p = 0.470). Furthermore, segmental resection did not prolong patient survival time compared with wedge resection in different subgroup analyses on the basis of histology, age, and tumor size (all p > 0.05). Finally, the same results were obtained via multivariate Cox analysis (OS: p = 0.153; HR = 1.21; CSS: p = 0.351, HR = 1.32). Sublobar resection could be considered for patients with early-stage typical or atypical pulmonary carcinoid, provided that a rigorous lymph node evaluation is conducted. If the tumor is distant from the pulmonary hilum, either segmentectomy or wedge resection may be performed depending on the specific location of the tumor and the clinical condition of the patient., (© 2024. The Author(s).)

Purpose: Kinase interacting with stathmin (KIS) is a serine/threonine kinase involved in RNA processing and protein phosphorylation. Increasing evidence has suggested its involvement in cancer progression. The aim of this study was to investigate the role of KIS in the development of lung adenocarcinoma (LUAD). Dual luciferase assay was used to explore the relationship between KIS and SOX4, and its effect on ID1/β-catenin pathway., Methods: Real-time qPCR and western blot were used to assess the levels of KIS and other factors. Cell proliferation, migration, and invasion were monitored, and xenograft animal model were established to investigate the biological functions of KIS in vitro and in vivo., Results: In the present study, KIS was found to be highly expressed in LUAD tissues and cell lines. KIS accelerated the proliferative, migratory and invasive abilities of LUAD cells in vitro, and promoted the growth of LUAD in a mouse tumor xenograft model in vivo. Mechanistically, KIS activated the β-catenin signaling pathway by modulating the inhibitor of DNA binding 1 (ID1) and was transcriptionally regulated by SOX4 in LUAD cells., Conclusion: KIS, a target of SOX4, regulates the ID1-mediated enhancement of β-catenin to facilitate LUAD cell invasion and metastasis., (© 2024. The Author(s).)

Introduction: Lung cancer is the most common cancer worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Chemotherapy, a mainstay modality for NSCLC, has demonstrated restricted effectiveness due to the emergence of chemo-resistance and systemic side effects. Studies have indicated that combining chemotherapy with phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), can enhance efficacy of therapy. In this work, an aminated mesoporous graphene oxide (rPGO)-protoporphyrin IX (PPIX)-hyaluronic acid (HA)@Osimertinib (AZD) nanodrug delivery system (rPPH@AZD) was successfully developed for combined chemotherapy/phototherapy for NSCLC., Methods: A pH/hyaluronidase-responsive nanodrug delivery system (rPPH@AZD) was prepared using mesoporous graphene oxide. Its morphology, elemental composition, surface functional groups, optical properties, in vitro drug release ability, photothermal properties, reactive oxygen species production, cellular uptake and cell viability were evaluated. In addition, the in vivo therapeutic effect, biocompatibility, and imaging capabilities of rPPH@AZD were verified by a tumor-bearing mouse model., Results: Aminated mesoporous graphene oxide (rPGO) plays a role as a drug delivery vehicle owing to its large specific surface area and ease of surface functionalization. rPGO exhibits excellent photothermal conversion properties under laser irradiation, while PPIX acts as a photosensitizer to generate singlet oxygen. AZD acts as a small molecule targeted drug in chemotherapy. In essence, rPPH@AZD shows excellent photothermal and fluorescence imaging effects in tumor-bearing mice. More importantly, in vitro and in vivo results indicate that rPPH@AZD can achieve hyaluronidase/pH dual response as well as combined chemotherapy/PTT/PDT anti-NSCLC treatment., Conclusion: The newly prepared rPPH@AZD can serve as a promising pH/hyaluronidase-responsive nanodrug delivery system that integrates photothermal/fluorescence imaging and chemo/photo combined therapy for efficient therapy against NSCLC., Competing Interests: All authors have no conflicts of interest to disclose for this work., (© 2024 Zhang et al.)

Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Electrochemical biosensors have emerged as powerful tools for the ultrasensitive detection of lung cancer biomarkers like carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and alpha fetoprotein (AFP). This review comprehensively discusses the progress and potential of nanocomposite-based electrochemical biosensors for early lung cancer diagnosis and prognosis. By integrating nanomaterials like graphene, metal nanoparticles, and conducting polymers, these sensors have achieved clinically relevant detection limits in the fg/mL to pg/mL range. We highlight the key role of nanomaterial functionalization in enhancing sensitivity, specificity, and antifouling properties. This review also examines challenges related to reproducibility and clinical translation, emphasizing the need for standardization of fabrication protocols and robust validation studies. With the rapid growth in understanding lung cancer biomarkers and innovations in sensor design, nanocomposite electrochemical biosensors hold immense potential for point-of-care lung cancer screening and personalized therapy guidance. Realizing this goal will require strategic collaboration among material scientists, engineers, and clinicians to address technical and practical hurdles. Overall, this work provides valuable insight for developing next-generation smart diagnostic devices to combat the high mortality of lung cancer.

Lung cancer is a malignant tumor with high mortality and drug resistance. Therefore, it is urgent to explore natural and nontoxic drugs to treat lung cancer. In this study, the natural active ingredient AANL extracted from Agrocybe aegirita was used to modify nanoselenium by an oxidation-reduction method. Transmission electron microscope detection and infrared spectroscopy showed that a novel selenium nanocomposite named AANL-SeNPs was successfully prepared. The results of nanoscale characterization showed that AANL-SeNPs had good stability and uniform dispersion in aqueous solution by zeta potential and spectrum analysis. At the cellular level, we found that AANL-SeNPs significantly inhibited the cell viability of lung cancer cells, and the cell inhibition rate of 60 nM AANL-SeNPs was 39 % in H157 cells, 67 % in H147 cells, and 62 % in A549 cells. The IC50 value of AANL-SeNPs was 51.85 nM in A549 cells and 81.57 nM in H157 cells. Moreover, AANL-SeNPs could inhibit the cell proliferation and migration, and enhance the sensitivity of lung cancer cells to osimertinib and has no toxic to normal cells. In vivo, AANL-SeNPs significantly slowed tumor growth in tumor-bearing mice by establishing a subcutaneous transplantation tumor model for lung cancer, and the tumor size was smaller and was reduced about 79 % in 2 mg/kg AANL-SeNPs group compared with PBS group. Mechanistically, a total of 38 differentially expressed proteins were identified by data-independent acquisition mass spectrometry. A significantly upregulated protein, CDC-like kinase 2 (CLK2), was screened and validated for further analysis, which showed that the expression levels of CLK2 were increased in H157 and H1437 cells after AANL-SeNPs treatment. The results obtained in this study suggest that a novel selenium nanocomposite AANL-SeNPs, which inhibits lung cancer by upregulating the expression of CLK2., 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: There is still a very high morbidity and mortality rate for patients undergoing peritoneal dialysis (PD). The advanced lung cancer inflammation index (ALI) has been demonstrated to be associated with the prognosis in multiple types of cancers. Like in cancer, systemic chronic low-grade inflammation is one of the distinguishing features of PD patients. Therefore, we aimed to investigate the relationships between the ALI and all-cause and cardiovascular disease (CVD) mortality in PD patients., Methods: Patients who started PD at Shaoxing People's Hospital between 1 January 2013 and 31 December 2020 (n = 277) were recruited and followed up until 1 July 2023. They were divided into high-ALI group and low-ALI group according to the median of ALI. Kaplan-Meier curves and multivariate Cox regression analyses were used to assess the associations between the ALI and all-cause and CVD mortality. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated to determine the predictive power of the ALI for all- cause and CVD mortality., Results: During the median follow-up of 40.50 months (interquartile range, 26.42-59.77 months), a total of 55 patients died, 31 of whom died due to CVD. Kaplan-Meier curves revealed that patients in the low-ALI group had significantly lower cumulative and cardiovascular cumulative survival rates than did those in the high-ALI group (all P < 0.001). After we corrected for confounders, the risk of all-cause and CVD mortality was significantly greater in the low-ALI group than in the high-ALI group [hazard ratio (HR) 1.944, 95% confidence interval (CI) 1.068-3.540, P = 0.030, and HR 2.672, 95% CI 1.188-6.009, P = 0.017, respectively]. The predictive value of ALI (AUC = 0.708, 95% CI 0.630-0.786, P < 0.001) for all-cause mortality was superior to albumin (AUC = 0.644, 95% CI 0.556-0.726, P < 0.001), body mass index (AUC = 0.581, 95% CI 0.496-0.659, P = 0.069) and neutrophil-to-lymphocyte ratio (AUC = 0.675, 95% CI 0.596-0.754, P < 0.001)., Conclusion: A lower ALI is an independent risk factor for all-cause and cardiovascular mortality in PD patients. The ALI may be an effective indicator for predicting outcomes in PD patients., (© 2024. The Author(s).)

PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kong 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.)

Background: Non-small cell lung cancer (NSCLC) is a prevalent and heterogeneous disease with significant genomic variations between the early and advanced stages. The identification of key genes and pathways driving NSCLC tumor progression is critical for improving the diagnosis and treatment outcomes of this disease., Methods: In this study, we conducted single-cell transcriptome analysis on 93,406 cells from 22 NSCLC patients to characterize malignant NSCLC cancer cells. Utilizing cNMF, we classified these cells into distinct modules, thus identifying the diverse molecular profiles within NSCLC. Through pseudotime analysis, we delineated temporal gene expression changes during NSCLC evolution, thus demonstrating genes associated with disease progression. Using the XGBoost model, we assessed the significance of these genes in the pseudotime trajectory. Our findings were validated by using transcriptome sequencing data from The Cancer Genome Atlas (TCGA), supplemented via LASSO regression to refine the selection of characteristic genes. Subsequently, we established a risk score model based on these genes, thus providing a potential tool for cancer risk assessment and personalized treatment strategies., Results: We used cNMF to classify malignant NSCLC cells into three functional modules, including the metabolic reprogramming module, cell cycle module, and cell stemness module, which can be used for the functional classification of malignant tumor cells in NSCLC. These findings also indicate that metabolism, the cell cycle, and tumor stemness play important driving roles in the malignant evolution of NSCLC. We integrated cNMF and XGBoost to select marker genes that are indicative of both early and advanced NSCLC stages. The expression of genes such as CHCHD2, GAPDH, and CD24 was strongly correlated with the malignant evolution of NSCLC at the single-cell data level. These genes have been validated via histological data. The risk score model that we established (represented by eight genes) was ultimately validated with GEO data., Conclusion: In summary, our study contributes to the identification of temporal heterogeneous biomarkers in NSCLC, thus offering insights into disease progression mechanisms and potential therapeutic targets. The developed workflow demonstrates promise for future applications in clinical practice., (© 2024. The Author(s).)

Background: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC., Methods: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison., Results: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS., Conclusions: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio., (© 2024. The Author(s).)

Introduction: This study is a retrospective study. This study aims to explore the association between lobectomy in lung cancer patients and subsequent compensatory lung growth (CLG), and to identify factors that may be associated with variations in CLG., Methods: 207 lung cancer patients who underwent lobectomy at Yunnan Cancer Hospital between January 2020 and December 2020. All patients had stage IA primary lung cancer and were performed by the same surgical team. And computed tomography examinations were performed before and 1 y postoperatively. Based on computed tomography images, the volume of each lung lobe was measured using computer software and manual, the radiological lung weight was calculated. And multiple linear regressions were used to analyze the factors related to the increase in postoperative lung weight., Results: One year after lobectomy, the radiological lung weight increased by an average of 112.4 ± 20.8%. Smoking history, number of resected lung segments, preoperative low attenuation volume, intraoperative arterial oxygen partial pressure/fraction of inspired oxygen ratio and postoperative visual analog scale scores at 48 h were significantly associated with postoperative radiological lung weight gain., Conclusions: Our results suggest that CLG have occurred after lobectomy in adults. In addition, anesthetists should maintain high arterial oxygen partial pressure/fraction of inspired oxygen ratio during one-lung ventilation and improve acute postoperative pain to benefit CLG., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The latest developments in deep learning have demonstrated the importance of CT medical imaging for the classification of pulmonary nodules. However, challenges remain in fully leveraging the relevant medical annotations of pulmonary nodules and distinguishing between the benign and malignant labels of adjacent nodules. Therefore, this paper proposes the Nodule-CLIP model, which deeply mines the potential relationship between CT images, complex attributes of lung nodules, and benign and malignant attributes of lung nodules through a comparative learning method, and optimizes the model in the image feature extraction network by using its similarities and differences to improve its ability to distinguish similar lung nodules. Firstly, we segment the 3D lung nodule information by U-Net to reduce the interference caused by the background of lung nodules and focus on the lung nodule images. Secondly, the image features, class features, and complex attribute features are aligned by contrastive learning and loss function in Nodule-CLIP to achieve lung nodule image optimization and improve classification ability. A series of testing and ablation experiments were conducted on the public dataset LIDC-IDRI, and the final benign and malignant classification rate was 90.6%, and the recall rate was 92.81%. The experimental results show the advantages of this method in terms of lung nodule classification as well as interpretability., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To investigate relationships between various symptoms occurring 1-2 and 5-6 days following days after thoracoscopic surgery, to identify core symptoms, and to monitor changes in core symptoms over time following lung cancer thoracoscopic surgery., Methods: We evaluated symptoms using the Anderson Symptom Scale (Chinese version) and the Lung Cancer-Specific Symptoms Template in 214 lung cancer patients hospitalized in the Department of Thoracic Surgery of a provincial hospital in Jiangsu Province from March 2023 to September 2023. Data was collected at 1-2 days and 5-6 days postoperatively. Symptom networks were constructed for each time point, and centrality indicators were analyzed to identify core symptoms while controlling for influencing factors., Results: According to the network analysis, fatigue (rs = 26.00、rc = 0.05、rb = 1.02) had the highest strength, closeness, and betweenness in the symptom network 1-2 days after lung cancer surgery. At 5-6 days after surgery, shortness of breath (rs = 27.00) emerged as the symptom with the highest strength, fatigue (rc = 0.04) had the highest closeness, and cough (rb = 1.08) ranked highest in betweenness within the symptom network., Conclusion: Fatigue stands out as the most core symptom in the network 1-2 days after lung cancer surgery. Shortness of breath, fatigue and cough are the most core symptoms in the symptom network 5-6 days after surgery. Therefore, clinical staff can improve the postoperative symptom experience of lung cancer patients by developing symptom management programmes tailored to these core symptoms., 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 Ltd. All rights reserved.)

Objectives: 18 F-fluorodeoxyglucose (FDG) PET/CT has been widely used for the differential diagnosis of cancer. Semi-quantitative standardized uptake value (SUV) is known to be affected by multiple factors and may make it difficult to differentiate between benign and malignant lesions. It is crucial to find reliable quantitative metabolic parameters to further support the diagnosis. This study aims to evaluate the value of the quantitative metabolic parameters derived from dynamic FDG PET/CT in the differential diagnosis of lung cancer and predicting epidermal growth factor receptor (EGFR) mutation status., Methods: We included 147 patients with lung lesions to perform FDG PET/CT dynamic plus static imaging with informed consent. Based on the results of the postoperative pathology, the patients were divided into benign/malignant groups, adenocarcinoma (AC)/squamous carcinoma (SCC) groups, and EGFR-positive (EGFR+)/EGFR-negative (EGFR-) groups. Quantitative parameters including K 1 , k 2 , k 3 , and K i of each lesion were obtained by applying the irreversible two-tissue compartmental modeling using an in-house Matlab software. The SUV analysis was performed based on conventional static scan data. Differences in each metabolic parameter among the group were analyzed. Wilcoxon rank-sum test, independent-samples T-test, and receiver-operating characteristic (ROC) analysis were performed to compare the diagnostic effects among the differentiated groups. P < 0.05 were considered statistically significant for all statistical tests., Results: In the malignant group (N = 124), the SUV max , k 2 , k 3 , and K i were higher than the benign group (N = 23), and all had-better performance in the differential diagnosis (P < 0.05, respectively). In the AC group (N = 88), the SUV max , k 3 , and K i were lower than in the SCC group, and such differences were statistically significant (P < 0.05, respectively). For ROC analysis, K i with cut-off value of 0.0250 ml/g/min has better diagnostic specificity than SUV max (AUC = 0.999 vs. 0.70). In AC group, 48 patients further underwent EGFR testing. In the EGFR (+) group (N = 31), the average K i (0.0279 ± 0.0153 ml/g/min) was lower than EGFR (-) group (N = 17, 0.0405 ± 0.0199 ml/g/min), and the difference was significant (P < 0.05). However, SUV max and k 3 did not show such a difference between EGFR (+) and EGFR (-) groups (P>0.05, respectively). For ROC analysis, the K i had a cut-off value of 0.0350 ml/g/min when predicting EGFR status, with a sensitivity of 0.710, a specificity of 0.588, and an AUC of 0.674 [0.523-0.802]., Conclusion: Although both techniques were specific, Ki had a greater specificity than SUVmax when the cut-off value was set at 0.0250 ml/g/min for the differential diagnosis of lung cancer. At a cut-off value of 0.0350 ml/g/min, there was a 0.710 sensitivity for EGFR status prediction. If EGFR testing is not available for a patient, dynamic imaging could be a valuable non-invasive screening method., (© 2024. The Author(s).)

Recent studies have indicated that dysregulation of the Hippo/Yes-associated protein (YAP) axis is associated with tumor progression and therapy resistance in various cancer types, including lung adenocarcinoma (LUAD). Understanding the regulation of Hippo signaling in LUAD is of great significance. Elevated levels of TRIB3, a pseudo kinase, have been observed in certain lung malignancies and are associated with an unfavorable prognosis. Our research aims to investigate whether increased TRIB3 levels enhance the malignant characteristics of LUAD cells and tumor progression through its interaction with the Hippo signaling pathway. In this study, we reported a positive correlation between elevated expression of TRIB3 and LUAD progression. Additionally, TRIB3 has the ability to enhance TEAD luciferase function and suppress Hippo pathway activity. Moreover, TRIB3 increases total YAP protein levels and promotes YAP nuclear localization. Mechanistic experiments revealed that TRIB3 directly interacts with large tumor suppressor kinase 1 (LATS1), thereby suppressing Hippo signaling. Moreover, the decrease in METTL3-mediated N6-methyladenosine modification of TRIB3 results in a substantial elevation of its expression levels in LUAD cells. Collectively, our research unveils a novel discovery that TRIB3 enhances the growth and invasion of LUAD cells by interacting with LATS1 and inhibiting the Hippo signaling pathway. TRIB3 may serve as a potential biomarker for an unfavorable prognosis and a target for novel treatments in YAP-driven lung cancer., (© 2024 Wiley Periodicals LLC.)

LINC00857 is frequently dysregulated in varying cancers, which in turn exerts carcinogenic effects; however, its DNA methylation status in promoter region and molecular mechanisms underlying the progression of lung adenocarcinoma (LUAD) remain rarely understood. Through bioinformatics analysis, we examined the expression state and methylation site of LINC00857 in LUAD and further investigated the properties of LINC00857 as a competitive endogenous RNA in the cancer progression. The current study revealed that the overexpression of LINC00857 in LUAD tissue and cells was mainly caused by the hypomethylation of the promoter region. LINC00857 knockdown prominently reduced cell proliferation, impeded cell migration and invasion, and restrained lymph node metastasis, with enhancing radiosensitivity. The effects of LINC00857 on tumor growth were also investigated in nude mice models. Subsequently, the downstream factors, miR-486-5p and NEK2, were screened, and the putative regulatory axis was examined. Overall, the regulatory effect of methylation-mediated LINC00857 overexpression on miR-486-5p/NEK2 axis may be a new mechanism for LUAD progression., (© 2024 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to evaluate and compare the performances of whole-lesion iodine map histogram analysis to those of single-slice spectral computed tomography (CT) parameters in discriminating between low-to-moderate grade invasive non-mucinous pulmonary adenocarcinoma (INMA) and high-grade INMA according to the novel International Association for the Study of Lung Cancer grading system of INMA., Materials and Methods: Sixty-one patients with INMA (34 with low-to-moderate grade [i.e., grade I and grade II] and 27 with high grade [i.e., grade III]) were evaluated with spectral CT. There were 28 men and 33 women, with a mean age of 56.4 ± 10.5 (standard deviation) years (range: 29-78 years). The whole-lesion iodine map histogram parameters (mean, standard deviation, variance, skewness, kurtosis, entropy, and 1st, 10th, 25th, 50th, 75th, 90th, and 99th percentile) were measured for each INMA. In other sessions, by placing regions of interest at representative levels of the tumor and normalizing them, spectral CT parameters (iodine concentration and normalized iodine concentration) were obtained. Discriminating capabilities of spectral CT and histogram parameters were assessed and compared using area under the ROC curve (AUC) and logistic regression models., Results: The 1st, 10th, and 25th percentiles of the iodine map histogram analysis, and iodine concentration and normalized iodine concentration of single-slice spectral CT parameters were significantly different between high-grade and low-to-moderate grade INMAs (P < 0.001 to P = 0.002). The 1st percentile of histogram parameters (AUC, 0.84; 95% confidence interval [CI]: 0.73-0.92) and iodine concentration (AUC, 0.78; 95% CI: 0.66-0.88) from single-slice spectral CT parameters had the best performance for discriminating between high-grade and low-to-moderate grade INMAs. At ROC curve analysis no significant differences in AUC were found between histogram parameters (AUC = 0.86; 95% CI: 0.74-0.93) and spectral CT parameters (AUC = 0.81; 95% CI: 0.74-0.93) (P = 0.60)., Conclusion: Both whole-lesion iodine map histogram analysis and single-slice spectral CT parameters help discriminate between low-to-moderate grade and high-grade INMAs according to the novel International Association for the Study of Lung Cancer grading system, with no differences in diagnostic performances., Competing Interests: Declaration of Competing Interest The authors declare no competing interests in relation with this study., (Copyright © 2023 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Penpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer., Methods: This multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18-75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m 2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1-49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993)., Findings: Between Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0-41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8--9·6 vs 4·2 months, 95% CI 4·2-4·3; HR 0·43, 95% CI 0·33-0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7-9·7 vs 4·2 months, 4·1-4·3; HR 0·37, 0·27-0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group., Interpretation: Penpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease., Funding: The National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A high level of reduced glutathione is a major factor contributing to the radioresistance observed in solid tumors. To address this radioresistance associated with glutathione, a cinnamaldehyde (CA) polymer prodrug, referred to as PDPCA, is fabricated. This prodrug is created by synthesizing a pendent CA prodrug with acetal linkages in a hydrophobic block, forming a self-assembled into a core-shell nanoparticle in aqueous media. Additionally, it encapsulates all-trans retinoic acid (ATRA) for synchronous delivery, resulting in PDPCA@ATRA. The PDPCA@ATRA nanoparticles accumulate reactive oxygen species through both endogenous and exogenous pathways, enhancing ferroptosis by depleting glutathione. This approach demonstrates efficacy in overcoming tumor radioresistance in vivo and in vitro, promoting the ferroptosis, and enhancing the cytotoxic T lymphocyte (CTL) response for lung tumors to anti-PD-1 (αPD-1) immunotherapy. Furthermore, this study reveals that PDPCA@ATRA nanoparticles promote ferroptosis through the NRF2-GPX4 signaling pathway, suggesting the potential for further investigation into the combination of radiotherapy and αPD-1 immune checkpoint inhibitors in cancer treatment., (© 2024 Wiley‐VCH GmbH.)

Integrin alpha L (ITGAL), a member of the integrin family, is associated with carcinogenesis and immune regulation. However, the biological functions of ITGAL in lung adenocarcinoma (LUAD) remain poorly understood. In this study, we utilized the TCGA dataset to analyse ITGAL mRNA expression in LUAD and examined its correlation with clinical prognosis. Three-dimensional (3D) Matrigel culture, 5-bromodeoxyuridine (BrdU) ELISA, wound-healing migration and cell adherence assays were used to demonstrate the potential role of ITGAL in LUAD progression. Additionally, we analysed single-cell sequencing data of LUAD to determine the expression and biological function of ITGAL. Our research revealed that the expression of ITGAL in LUAD samples is an independent predictor of prognosis. Patients with high expression of ITGAL had significantly better overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) compared to the low-expression group. Meanwhile, the expression of ITGAL suppressed malignant progression in LUAD cells. Functional enrichment analyses showed that ITGAL was significantly correlated with cell immune response and immune checkpoint, consistent with the analysis of single-cell sequencing in paired samples of normal and tumour. Furthermore, we confirmed that ITGAL expression affect the tumour microenvironment (TME) through regulation of the expression of cytokines in NK cells of LUAD. In summary, ITGAL is a prognostic biomarker for LUAD patients, and it repressed malignant progression in LUAD cells. Moreover, ITGAL expression also enhanced the effect of immunotherapy and may be an important target in LUAD therapy., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)