Abstract
Clear cell renal cell carcinoma (ccRCC) is a lethal urological malignancy. DNA methylation is involved in the regulation of ccRCC occurrence and progression. This study aimed to establish a prognostic model based on DNA methylation to predict the overall survival (OS) of patients with ccRCC. To create this model, we used the transcriptome and DNA methylation data of patients with ccRCC from The Cancer Genome Atlas (TCGA) database. We then used the MethylMix R package to identify methylation-driven genes, and LASSO regression and multivariate Cox regression analyses established the prognostic risk model, from which we derived risk scores. We incorporated these risk scores and clinical parameters to develop a prognostic nomogram to predict 3-, 5-, and 7-year overall survival, and its predictive power was validated using the ArrayExpress cohort. These analyses identified six methylation-driven genes (SAA1, FUT6, SPATA18, SHROOM3, AJAP1, and NPEPL1) that produced risk scores, which were sorted into high- and low-risk patient groups. These two groups differed in nomogram-predicted prognosis, the extent of immune cell infiltration, tumor mutational burden, and expected response to additional therapies. In conclusion, we established a nomogram based on six DNA methylation-driven genes with excellent accuracy for prognostic prediction in ccRCC patients. This nomogram model might provide novel insights into the epigenetic mechanism and individualized treatment of ccRCC.