A radiotherapy resistance-related prognostic signature predicts survival and the immune landscape in rectal cancer

作者：Jiang T, Zhu L, Jiang R, Jin H, Yuan S · 发表于：Translational cancer research · 年份：2026 · DOI：10.21037/tcr-2026-0554 · 被引用次数：31

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 CUTA, IZUMO2, PALB2, and PSCA was established. The signature effect...