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P21-activated kinases (PAKs) are serine/threonine protein kinases that contribute to several cellular processes. Here, we aimed to determine the prognostic value of PAK1 and its correlation with the clinicopathological characteristics and five-year survival rates in patients with non-small cell lung cancer (NSCLC). We evaluated PAK1 mRNA and protein expression in NSCLC cells and resected tumor specimens, as well as in healthy human bronchial epithelial cells and adjacent healthy lung tissues, respectively, for effective comparison. Immunohistochemical tissue microarray analysis of 201 NSCLC specimens showed the correlation of PAK1 expression with clinicopathological characteristics. The mRNA and protein expression of PAK1 were 2.9- and 4.3-fold higher in six of seven NSCLC cell types and human tumors (both, < 0.001) than in healthy human bronchial epithelial BEAS-2B cells and adjacent healthy lung tissues, respectively. Decreased survival was significantly associated with PAK1 overexpression in the entire cohort (χ = 8.48, = 0.0036), men (χ = 17.1, < 0.0001), and current and former smokers (χ = 19.2, < 0.0001). Notably, epidermal growth factor receptor (EGFR) mutation-positive lung cancer patients with high PAK1 expression showed higher mortality rates than those with low PAK1 expression (91.3% vs. 62.5%, = 0.02). Therefore, PAK1 overexpression could serve as a molecular target for the treatment of EGFR mutation-positive lung cancer, especially among male patients and current/former smokers.
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http://dx.doi.org/10.3390/molecules25235588 | 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.