A five-gene methylation signature predicts overall survival of patients with clear cell renal cell carcinoma

Abstract

Background: In this study, we aimed to screen methylation signatures associated with the prognosis of patients with clear cell renal cell carcinoma (ccRCC). Methods: Gene expression and methylation profiles of ccRCC patients were downloaded from publicly available databases, and differentially expressed genes (DEGs)-differentially methylated genes (DMGs) were obtained. Subsequently, gene set enrichment and transcription factor (TF) regulatory network analyses were performed. In addition, a prognostic model was constructed and the relationship between disease progression and immunity was analyzed. Results: A total of 23 common DEGs-DMGs were analyzed, among which 14 DEGs-DMGs were obtained with a cutoff value of PCC < 0 and p < 0.05. The enrichment analysis showed that the 14 DEGs-DMGs were enriched in three GO terms and three KEGG pathways. In addition, a total of six TFs were shown to be associated with the 14 DEGs-DMGs, including RP58, SOX9, NF-κB65, ATF6, OCT, and IK2. A prognostic model using five optimized DEGs-DMGs which efficiently predicted survival was constructed and validated using the GSE105288 dataset. Additionally, four types of immune cells (NK cells, macrophages, neutrophils, and cancer-associated fibroblasts), as well as ESTIMATE, immune, and stromal scores were found to be significantly correlated with ccRCC progression (normal, primary, and metastasis) in addition to the five optimized DEGs-DMGs. Conclusion: A five-gene methylation signature with the predictive ability for ccRCC prognosis was investigated in this study, consisting of CCNB2, CDKN1C, CTSH, E2F2, and ERMP1. In addition, potential targets for methylation-mediated immunotherapy were highlighted.