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Lung cancer is the leading cause of cancer-related death worldwide, and the complex molecular mechanisms underlying its development, particularly the role of alternative splicing (AS) in different subtypes, remain poorly understood. In this study, we performed RNA sequencing of 178 lung cancer patients and conducted a comprehensive analysis of the transcriptomic landscape with a focus on AS. We identified robust lung cancer- and subtype-specific AS biomarkers that were consistently effective in both tissue samples and cancer cell lines. Notably, several of these biomarkers also serve as critical regulators in lung cancer progression. Our regulatory network analysis, with a focus on RNA-binding proteins, revealed QKI and SR proteins as key splicing factors. Specifically, QKI was found to modulate the splicing of exon 15, a cancer-specific AS biomarker, while SRSF1 regulated the splicing of exon 14, a subtype-specific AS biomarker. Our study provides valuable insights into key AS events and their regulatory mechanisms in lung cancer, paving the way for potential therapeutic targets.
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http://dx.doi.org/10.1016/j.omtn.2025.102681 | DOI Listing |
Biochem Soc Trans
September 2025
Department of Biochemistry, McGill University, Montréal, QC, Canada.
The MET receptor tyrosine kinase is a pivotal regulator of cellular survival, motility, and proliferation. Mutations leading to skipping of exon 14 (METΔex14) within the juxtamembrane domain of MET impair receptor degradation and prolong oncogenic signaling, contributing significantly to tumor progression across multiple cancer types. METΔex14 mutations are associated with aggressive clinical behavior, therapeutic resistance, and poor outcomes.
View Article and Find Full Text PDFPLoS One
September 2025
Institute of Computational Science and Technology, Guangzhou University, Guangzhou, China.
MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology, yet their spatial dynamics within tumor microenvironments (TMEs) remain underexplored due to technical limitations in current spatial transcriptomics (ST) technologies. To address this gap, we present STmiR, a novel XGBoost-based framework for spatially resolved miRNA activity prediction. STmiR integrates bulk RNA-seq data (TCGA and CCLE) with spatial transcriptomics profiles to model nonlinear miRNA-mRNA interactions, achieving high predictive accuracy (Spearman's ρ > 0.
View Article and Find Full Text PDFPLoS One
September 2025
Biobank of Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
Heart failure (HF) and lung cancer (LC) often coexist, yet their shared molecular mechanisms are unclear. We analyzed transcriptome data from the NCBI Gene Expression Omnibus (GEO) database (GSE141910, GSE57338) to identify 346 HF‑related differentially expressed genes (DEGs), then combined weighted gene co-expression network analysis (WGCNA) pinpointed 70 hub candidates. Further screening of these 70 hub candidates in TCGA lung cancer cohorts via LASSO, Random Forest, and multivariate Cox regression suggested CYP4B1 as the only independent prognostic marker.
View Article and Find Full Text PDFPLoS One
September 2025
Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Volumetric modulated arc therapy (VMAT) for lung cancer involves complex multileaf collimator (MLC) motion, which increases sensitivity to interplay effects with tumour motion. Current dynamic conformal arc methods address this issue but may limit the achievable dose distribution optimisation compared with standard VMAT. This study examined the clinical utility of a VMAT technique with monitor unit limits (VMATliMU) to mimic conformal arc delivery and reduce interplay effects while maintaining plan quality.
View Article and Find Full Text PDFJAMA Netw Open
September 2025
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Importance: Patients with advanced cancer frequently receive broad-spectrum antibiotics, but changing use patterns across the end-of-life trajectory remain poorly understood.
Objective: To describe the patterns of broad-spectrum antibiotic use across defined end-of-life intervals in patients with advanced cancer.
Design, Setting, And Participants: This nationwide, population-based, retrospective cohort study used data from the South Korean National Health Insurance Service database to examine broad-spectrum antibiotic use among patients with advanced cancer who died between July 1, 2002, and December 31, 2021.