We found that DNA hypermethylation of CST6 and LAD1 in primary RCC tumor tissue is significantly associated with the PFS of patients receiving anti-VEGF-based medication as a first-line therapy and also the OS of patients sequentially treated with anti-VEGF targeted drugs and mTOR inhibitors in second- and third-line therapy. This evidence concerns the gene CST6 and renal cell adenocarcinoma.