biostudies-literatureUnknown16Li Z<h4>Background</h4>Clear cell renal cell carcinoma (ccRCC) exhibits marked heterogeneity and variable benefit from immune checkpoint inhibitors (ICIs). Post-translational modifications (PTMs) regulate immune signaling and tumor behavior, yet PTM-informed biomarkers for ccRCC remain underexplored.<h4>Methods</h4>We intersected immune-related genes, PTM-related genes, and differentially expressed genes in TCGA-KIRC to derive candidates and built a prognostic model across TCGA and E-MTAB-1980 using multiple algorithms, selecting a random survival forest-based post-translational modification-related signature (PTMRS) with the best performance. Prognostic value and independence were evaluated by time-dependent ROC, Kaplan-Meier, and multivariate Cox analyses. Tumor immune context was profiled bFrontiers in immunology1707375https://www.ebi.ac.uk/biostudies/studies/S-EPMC12702869biostudies-literatureIntegrative multi-omics analysis identifies a PTM-related immune signature and IRF9 as a driver in ccRCC.PMC12702869Li XHu SLi ZJiang SWang JfalseIntegrative multi-omics analysis identifies a PTM-related immune signature and IRF9 as a driver in ccRCC.<h4>Background</h4>Clear cell renal cell carcinoma (ccRCC) exhibits marked heterogeneity and variable benefit from immune checkpoint inhibitors (ICIs). Post-translational modifications (PTMs) regulate immune signaling and tumor behavior, yet PTM-informed biomarkers for ccRCC remain underexplored.<h4>Methods</h4>We intersected immune-related genes, PTM-related genes, and differentially expressed genes in TCGA-KIRC to derive candidates and built a prognostic model across TCGA and E-MTAB-1980 using multiple algorithms, selecting a random survival forest-based post-translational modification-related signature (PTMRS) with the best performance. Prognostic value and independence were evaluated by time-dependent ROC, Kaplan-Meier, and multivariate Cox analyses. Tumor immune context was profiled b2025-01-01T00:00:00Z20252026-06-06T04:19:26.927Z2026-05-25T03:12:01.618ZS-EPMC127028694140393510.3389/fimmu.2025.1707375