ISL1 and nonpapillary renal cell carcinoma: To further investigate and verify the biological functions of these TFs in ccRCC, we selected four TFs (HOXC5, VENTX, ISL1, and OTP) whose expression levels were significantly associated with worse overall survival in the TCGA-KIRC dataset, and binding sites were located in accessible chromatin regions, which were specific for kidney cancer and identified by ATAC-seq34 (Fig. 3a and Supplementary Fig. S3a).