en Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;"><span style="font-size:10pt"><span style="text-justify:newspaper"><span style="text-kashida-space:50%"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Background:</span></span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">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. </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Materials and Methods: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">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&ndash;Meier survival analysis. Gene function was explored using enrichment analysis and immune infiltration correlation. </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Results: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">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. </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Conclusion: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">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.</span></span></span></span></span></span></span></span></span></div> Lung neoplasms, exosomes, macrophages, biomarkers, radiotherapy, gene expression profiling. 979 986 http://ijrr.com/browse.php?a_code=A-10-1-1424&slc_lang=en&sid=1 S. Huang 7900319475328460033073 7900319475328460033073 No Department of Thoracic Surgery, Ningbo No.2 Hospital, Ningbo, Zhejiang Province, China J. Miao 7900319475328460033074 7900319475328460033074 No The Yangtze River Delta Biological Medicine Research and Development Center of Zhejiang Province, Yangtze Delta Region Institution of Tsinghua University, Hangzhou, Zhejiang, China Y. Gu guyyjiaxing@163.com 7900319475328460033075 7900319475328460033075 Yes Department of Respiratory and Critical Care Medicine, Jiaxing Second Hospital, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang Province, China