Individualized immune-related gene signature predicts immune status and oncologic outcomes in clear cell renal cell carcinoma patients

Abstract

ObjectiveTo develop an individualized immune-related gene signature that predicts oncologic outcomes and immune status of clear cell renal cell carcinoma (ccRCC). Materials and MethodsThe immune-related gene pair (IGP) index was constructed and validated based on pairwise comparison in 634 ccRCC patients. Association with overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) was evaluated by Kaplan-Meier analysis, univariate and multivariate cox regression survival analysis. Prognostic values of different risk models were compared using Harrell's C-index. ResultsThe IGP index of 17 gene pairs was an adverse independent risk factor in multivariate analyses for OS (hazard ratio [HR], 1.718; P = 0.001), PFI (HR, 1.550; P = 0.006), and DSS (HR, 2.201; P = 0.001) in ccRCC patients. It showed comparable prognostic accuracy with ccA/ccB signature (C-index for OS, 0.657 vs. 0.640; P = 0.686) and better intratumor homogeneity. Immunosuppressive immune cell, markers, and pathways were all enriched in high immune-risk tumors. The integrated immune-clinical prognostic score outperformed ccA/ccB signature and University of California Integrated Staging System risk model in terms of C-index for estimation of OS, PFI, and DSS (P < 0.001). ConclusionsThe proposed IGP index is a robust and promising biomarker for estimating oncologic outcomes in ccRCC. High immune-risk tumors are immunosuppressive.