The cuproptosis-associated 13 gene signature as a robust predictor for outcome and response to immune- and targeted-therapies in clear cell renal cell carcinoma

Cuproptosis, the newly identified form of regulatory cell death (RCD), results from mitochondrial proteotoxic stress mediated by copper and FDX1. Little is known about significances of cuproptosis in oncogenesis. Here we determined clinical implications of cuproptosis in clear cell renal cell carcinoma (ccRCC). Based on the correlation and survival analyses of cuproptosis-correlated genes in TCGA ccRCC cohort, we constructed a cuproptosis-associated 13 gene signature (CuAGS-13) score system. In both TCGA training and two validation cohorts, when patients were categorized into high- and low-risk groups according to a median score as the cutoff, the CuAGS-13 high-risk group was significantly associated with shorter overall survival (OS) and/or progression-free survival (PFS) independently (