Promising Epigenetic Biomarkers Associated With Cancer-Associated-Fibroblasts for Progression of Kidney Renal Clear Cell Carcinoma

Abstract

Kidney renal clear cell carcinoma (KIRC) is the most common malignant kidney tumor as its characterization of highly metastatic potential. Patients with KIRC are associated with poor clinical outcomes with limited treatment options. Up to date, the underlying molecular mechanisms of KIRC pathogenesis and progression are still poorly understood. Instead, particular features of Cancer-Associated Fibroblasts (CAFs) are highly associated with adverse outcomes of patients with KIRC, while the precise regulatory mechanisms at the epigenetic level of KIRC in governing CAFs remain poorly defined. Therefore, explore the correlations between epigenetic regulation and CAFs infiltration may help us better understand the molecular mechanisms behind KIRC progression, which may improve clinical outcomes and patients quality of life. In the present study, we identified a set of clinically relevant CAFs-related methylation-driven genes, NAT8, TINAG, and SLC17A1 in KIRC. Our comprehensive in silico analysis revealed that the expression levels of NAT8, TINAG, and SLC17A1 are highly associated with outcomes of patients with KIRC. Meanwhile, their methylation levels are highly correlates with the severity of KIRC. We suggest that the biomarkers might contribute to CAFs infiltration in KIRC. Taken together, our study provides a set of promising biomarkers which could predict the progression and prognosis of KIRC. Our findings could have potential prognosis and therapeutic significance in the progression of KIRC.