Pan-cancer patterns of cuproptosis markers reveal biologically and clinically relevant cancer subtypes

Cuproptosis is a newly discovered type of cell death triggered by copper accumulation. Here we exhibited the genetic profiles of 10 cuproptosis-associated genes (CuAGs) across 21 cancer types. Only 8.0% (627/7839) of tumors possessed at least 1 mutation on CuAGs, while the copy number amplifications or deletions on the alleles of CuAGs were ubiquitous. Generally, the expression of CuAGs showed heterogeneity across cancer types and the expression of CuAGs showed different correlations with MSI, TMB, immune and stromal features in different cancer types. Therefore, CuAGs were ubiquitously and heterogeneously dysregulated in pan-cancer. With a Non-negative Matrix Factorization method, we divided patients of each cancer type into cuproptosis-based subtypes, which showed a close but heterogeneous correlation with different biological and clinical features. Accordingly, we summarized all cancer types into four categories. The cancers in which cuproptosis subtypes correlated with MSI and TMB were annotated as Genomic disturbed. Those correlated with stromal scores were categorized as Stromal remolded. The others only associated with immune infiltration were labeled as Immune inhibited. A minor fraction of cancers not correlated with any biological indicators were marked as Cuproptosis inert. Together, we provided a pan-cancer overview of cuproptosis markers which revealed biologically and clinically relevant cancer subtypes in different cancers.