Clinical significance and immune microenvironment association of cuproptosis-related genes in pan-cancer

Recent studies highlight the important roles of cuproptosis in cancer cells. However, the roles of the cuproptosis-related genes (CRGs) in different cancers are still not fully understood. Comprehensive analysis was performed using open-source bioinformatic platforms to disclose the expression profiles, prognostic significance, genomic and epigenetic characteristics, immune microenvironment, and drug sensitivity of CRGs including FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, SLC31A1, MTF1, GLS, CDKN2A, HSPA4 and ATP7B. The colon cancer samples were further obtained to verify the correlation between CDKN2A expression and immune cell infiltration by fluorescence staining. We demonstrated the expression level, methylation and the copy number variant feature, as well as the prognostic significance of CRGs in pan-cancers. The expression of CRGs, especially PDHB, LITP1, ATP7B, HSPA4 and CDKN2A, was significantly correlated with pathological stages. The genetic alteration of CRGs was explored, and CDKN2A was the most frequently altered gene with alteration rate as high as 17% in 10,953 tumour patients. In addition, we revealed a relationship to the tumour immune microenvironment (TIME) and drug resistance in pan-cancer. Moreover, CDKN2A, which was closely correlated to pan-cancer prognosis, was especially analysed including TIME alteration, genomic heterogeneity and tumour stemness. Fluorescence images of colon cancer from different patients demonstrated a positive correlation between CDKN2A expression and the number of CD45⁺ immune cells. Our research has provided a comprehensive understanding of cuproptosis regulators and revealed potential prognostic biomarkers and therapeutic targets for cancers.