Department of Respiratory and Critical Care Medicine, Jiaxing Second Hospital, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang Province, China , guyyjiaxing@163.com
Abstract: (6 Views)
Background:Lung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer, has a poor prognosis in patients undergoing radiotherapy. M2 macrophage polarization and their derived exosomes play key roles in tumor progression, but their impact on LUAD prognosis remains unclear. This study aims to identify M2 macrophage-derived exosome-related genes associated with prognosis in radiotherapy-treated LUAD patients. Materials and Methods: Transcriptomic data from TCGA-LUAD, ExoRBase, ExoCarta, and GEO were analyzed. The CIBERSORT algorithm quantified immune cell infiltration, and differentially expressed genes (DEGs) were identified. Prognostic genes were screened via univariate Cox regression, LASSO regression, and Kaplan–Meier survival analysis. Gene function was explored using enrichment analysis and immune infiltration correlation. Results: A total of 2,592 DEGs were identified in LUAD, of which 17 were exosome-related and associated with M2 macrophages. Among these, FGR and MNDA emerged as key prognostic markers. High expression levels of both genes were associated with better outcomes: median overall survival of 45.2 months versus 28.7 months in the low-expression group. Improved progression-free interval and disease-specific survival were also observed. Multivariate analysis confirmed FGR and MNDA as independent prognostic indicators. Their high expression correlated with favorable radiotherapy response and enhanced immune infiltration, particularly of CD8⁺ T cells. Conclusion: FGR and MNDA, as M2 macrophage-derived exosome-related genes, are associated with favorable prognosis and enhanced radiotherapy response in LUAD. These biomarkers may offer novel insights into tumor immunity and therapeutic targeting in LUAD patients receiving radiotherapy.