Pan-cancer profiles of the cuproptosis gene set

Abstract A recent study has revealed a novel cell death pathway, called “cuproptosis”, a programmed cell death based on copper. A total of 12 genes were involved in the cuproptosis pathway, including 7 pro- cuproptosis genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, and PDHB) genes, 3 anti-cuproptosis genes (MTF1, GLS, and CDKN2A), and 2 key copper transporters ATP7B and SLC31A1. The insight into these cuproptosis genes in cancer is necessary to understand cuproptosis-related tumorigenesis and to develop the cuproptosis pathway as a potential therapeutic target for clinical cancer treatment. By mining multi-omic profiling data, we performed a comprehensive and systematic characterization of the cuproptosis of these 12 genes across more than 9000 samples of 33 types of cancer. This letter not only revealed diverse mechanisms of the gene expression regulations of the cuproptosis gene set in cancer but also analyzed the potential associations between cuproptosis and other common cancer pathways, providing an overall picture of cuproptosis in cancer for future reference. This study comprehensively clarified the genomic pan-cancer profiles of the cuproptosis gene set regarding the SNV, CNV, methylation, mRNA expression, pathway cross-talk, and miRNA regulations across 33 solid tumors. Our findings revealed that genomic alterations and miRNA-mRNA network-mediated ectopic expression of cuproptosis genes were involved in the activation of other cancer-related pathways and also identified KIRC as a potential cancer type that might be affected by cuproptosis. We think, as the rase of the cuproptosis cancer research, these in-time profiles will provide a genetic overview and useful information for future studies on the cuproptosis in cancers.