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Publicly accessible datasets from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed to identify differentially expressed genes associated with drug resistance and mitophagy. Functional enrichment analyses were conducted to investigate relevant biological pathways. A prognostic risk model was constructed using least absolute shrinkage and selection operator regression and validated via receiver operating characteristic (ROC) curve analysis and Kaplan\u2013Meier survival analysis. The final model incorporated 15 genes selected from an initial set of 121 differentially expressed genes and demonstrated moderate to high predictive accuracy for 1-, 2-, and 3-year overall survival (area under the ROC curve: 0.70\u20130.90). Kaplan\u2013Meier analysis revealed statistically significant differences in survival outcomes between high-risk and low-risk patient groups. Pathway enrichment analysis indicated that the selected genes were involved in actin cytoskeleton reorganization and antiviral immune responses. Differential expression of key genes within the model was confirmed through quantitative polymerase chain reaction assays. The resulting prognostic model enhances understanding of the molecular mechanisms underlying radiotherapy response in rectal neoplasms and may support individualized therapeutic decision-making in clinical oncology.<\/jats:p>","DOI":"10.1515\/biol-2025-1199","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T17:00:02Z","timestamp":1767027602000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrated genomic and clinical modeling for prognostic assessment of radiotherapy response in rectal neoplasms"],"prefix":"10.1515","volume":"20","author":[{"given":"Chen","family":"Li","sequence":"first","affiliation":[{"name":"China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, Chinese Center for Disease Control and Prevention , National Institute for Radiological Protection , Beijing , 100088 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Science and Technology of China , Hefei , 230026 , Anhui , P.R. China"},{"name":"High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology , Chinese Academy of Sciences , Hefei , P.R. China"},{"name":"Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology , Hefei Institutes of Physical Science, Chinese Academy of Sciences , Hefei , Anhui , 230031 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangxiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Second Affiliated Hospital , Zhejiang University, School of Medicine , Hangzhou , 310009 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Second Affiliated Hospital , Zhejiang University, School of Medicine , Hangzhou , 310009 , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongjian","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The First Medical Center , People\u2019s Liberation Army General Hospital , Beijing , 100853 , P.R. 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