Construction of A Novel Ferroptosis-related Prognostic Risk Signature for Survival Prediction in Clear Cell Renal Cell Carcinoma Patients.

Abstract

Targeted ferroptosis is a reliable therapy to inhibit tumor growth and enhance immunotherapy. This study generated a novel prognostic risk signature based on ferroptosis-related genes (FRGs), and explored the ability in clinic for clear cell renal cell carcinoma (ccRCC). The expression profile of mRNA and FRGs for ccRCC patients were exacted from The Cancer Genome Atlas (TCGA) database. A ferroptosis-related prognostic risk signature was constructed based on univariable and multivariable Cox-regression analysis. Kaplan-Meier (KM) survival curves and receiver operating characteristic (ROC) curves were performed to access prognostic value of riskscore. A nomogram integrating riskscore and clinical features was established to predict overall survival (OS). Based on differentially expressed genes between high- and low-OS groups with 5-year OS, function enrichment analyses and single-sample gene set enrichment analysis (ssGSEA) were investigated to immune status. A 9-FRGs prognostic risk signature was constructed based on 37 differentially expressed FRGs. ROC and KM curves showed that riskscore has excellent reliability and predictive ability; Cox regression disclosed the riskscore as an independent prognosis for ccRCC patients. Then, the C-index and calibration curve demonstrated the good performance of nomogram in training and validation cohort, and its predictive ability better than other features. Immune-related biological processes were enriched by function enrichment analysis, and the immune-related cells and functions were differential by ssGSEA between high- and low-OS groups. Our study identified and verified a novel 9-FRGs prognostic signature and nomogram to predict OS, providing a novel sight to explore targeted therapy of ferroptosis for ccRCC.