Systematic analysis of the aberrances and functional implications of cuproptosis in cancer

Cuproptosis is a novel form of cell death driven by a copper-dependent proteo-toxic stress response whose comprehensive landscape in tumors remains unclear. Here, we comprehensively characterized cuproptosis-related genes (CRGs) across 33 cancers using multi-omic data from The Cancer Genome Atlas (TCGA), showing complicated and diverse results in different cancers. We also explored the rela-tionships between CRGs and cancer metabolic patterns, pathway activity, and tumor microenvironment (TME), suggesting that they played critical roles in tumor progression and TME cell infiltration. We further established the cupropto-sis potential index (CPI) to reveal the functional roles of cuproptosis, and charac-terized multi-omic molecular features associated with cuproptosis. In clinical applications, we performed a combined analysis of the sensitivity of CRGs and CPI to drug response and immunotherapy. This study provides a rich resource for understanding cuproptosis, offering a broad molecular perspective for future functional and therapeutic studies of multiple cancer pathways mediated by cuproptosis.

Automated summary

Cuproptosis, a form of cell death driven by copper-dependent proteo-toxic stress response, was comprehensively characterized across 33 cancers using multi-omic data from TCGA. The study revealed complex and diverse results in different cancers and investigated the relationships between cuproptosis-related genes (CRGs) and cancer metabolic patterns, pathway activity, and tumor microenvironment. The establishment of the cuproptosis potential index (CPI) further revealed the functional roles of cuproptosis and characterized its molecular features. The study also conducted a combined analysis of CRGs and CPI in drug response and immunotherapy.