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

Urol J. 2022 May 22;19(4):289-299. doi: 10.22037/uj.v19i.6999.

Abstract

Purpose: 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).

Materials and methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / pathology
  • Ferroptosis* / genetics
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • Prognosis
  • RNA, Messenger
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor
  • RNA, Messenger