Pan-cancer analysis of cuproptosis-promoting gene signature from multiple perspectives

Cuproptosis is a newly discovered cell death form with a unique mechanism. Seven genes have been identified to facilitate the process. To explore the roles of cuproptosis in different cancers, we first used Gene Expression Profiling, Interactive Analysis, version 2, and cBioPortal to analyze expression, prognosis and mutation conditions in different cancers from The Cancer Genome Atlas (TCGA). Then, we conducted single sample gene set enrichment analysis to combine the signature of the cuproptosis-promoting genes for all TCGA cancers. Moreover, we performed a survival analysis to explore if cuproptosis-score could independently influence clinical outcomes. Next, we compared pathway enrichment, immune infiltration, gene set activity and gene mutation between different cuproptosis-score groups. Finally, based on the intersected genes from difference analysis and weighted gene co-expression network analysis, consensus clustering and Least Absolute Shrinkage and Selection Operator Cox regression were performed and nomograms were constructed. Cuproptosis-score was associated with a favorable prognosis in eight TCGA cancers. Cancer-associated fibroblasts, B cells, neutrophils and mast cells were generally less abundant, and ferroptosis activity was higher in high cuproptosis-score groups. The novel classifications could differentiate patients' overall survival, and the risk models could effectively predict patients' outcomes in kidney, renal clear cell carcinoma, liver hepatocellular carcinoma, mesothelioma and stomach adenocarcinoma. Cuproptosis activity was closely related to the prognosis of several cancers. Its effects on the immune microenvironment and its relationship with other cell death modes, especially ferroptosis, may become the focus of further research.