Construction and Validation of a Prognostic Nomogram for Clear Cell Renal Cell Carcinoma Based on DNA Methylation-driven Differentially Expressed Genes

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney cancer. This study aimed to establish a nomogram to predict ccRCC prognosis.Methods: By integrating DNA methylation (DNAm) data and gene expression profiles of ccRCC obtained from The Cancer Genome Atlas (TCGA), DNAm-driven genes were identified by differential and correlation analyses. Next, risk genes were selected by multiple algorithms (univariate Cox and Kaplan-Meier survival analyses) and various databases (TCGA, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and The Human Protein Atlas (HPA)). A risk score model was established by multivariate Cox analyses. ConsensusPathDB and Gene Set Enrichment Analysis (GSEA) were used to identify the biological functions of the selected genes. After comprehensively evaluating the clinical data, we established and assessed a dynamic nomogram available on a webserver.Results: In total, 220 differentially expressed DNAm-driven genes were identified, and five-gene signature (EPB41L4B, HHLA2, IFI16, CMTM3, and XAF1) was related to overall survival (OS). Next, we integrated the DNAm-driven genes into the prognostic risk score model and found that age, histologic grade, pathological stage, and risk level were correlated with OS in ccRCC patients. Based on these variables, a dynamic nomogram was established to predict the ccRCC prognosis. Finally, Functional enrichment analysis showed that the functions of these genes were relevant to immune reactions.Conclusions: We identified a 5 DNAm-driven gene signature whose altered status was highly correlated with ccRCC patient OS. We constructed a dynamic nomogram to provide individualized survival predictions for ccRCC patients.