ArticleTranslational cancer research2026
A radiotherapy resistance-related prognostic signature predicts survival and the immune landscape in rectal cancer.
Article in Translational cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Radiotherapy resistance remains a significant challenge in the management of locally advanced rectal cancer (LARC). To date, no universally applicable and reliable prognostic marker has been established for clinical practice. Thus, reliable biomarkers need to be identified and the molecular mechanisms underlying radiotherapy resistance need to be investigated to improve patient prognosis. The study aimed to identify a radiotherapy-related signature for evaluating radiotherapy response and predicting the overall survival (OS) of patients with rectal cancer. Methods: Multiple independent sources of transcriptomic datasets from The Cancer Genome Atlas (TCGA) (training cohort, n=154) and the Gene Expression Omnibus (GEO), including GSE35452 (containing radiotherapy response and non-response cohorts) and GSE87211 (validation cohort), were systematically integrated. A prognostic signature was developed by identifying radiotherapy-related genes through differential expression analysis and weighted gene correlation network analysis (WGCNA), followed by least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses. Functional enrichment, immune microenvironment characterization, and single-cell RNA sequencing (scRNA-seq) analyses were subsequently performed to explore the mechanisms underlying radiotherapy resistance. Results: A four-gene prognostic signature comprising Conclusions: This study developed and validated a four-gene signature for survival prediction in rectal cancer (RC). Functional enrichment and immune microenvironment characterization analyses indicated that the signature was associated with tumor heterogeneity and differential treatment responses in RC. The single-cell analysis indicated that
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