Impact of Cuproptosis-related markers on clinical status, tumor immune microenvironment and immunotherapy in colorectal cancer: A multi-omic analysis

BACKGROUND: Cuproptosis, a novel identified cell death form induced by copper, is characterized by aggregation of lipoylated mitochondrial enzymes and the destabilization of Fe–S cluster proteins. However, the function and potential clinical value of cuproptosis and cuproptosis-related biomarkers in colorectal cancer (CRC) remain largely unknown. METHODS: A comprehensive multi-omics (transcriptomics, genomics, and single-cell transcriptome) analysis was performed for identifying the influence of 16 cuproptosis-related markers on clinical status, molecular functions and tumor microenvironment (TME) in CRC. A novel cuproptosis-related scoring system (CuproScore) based on cuproptosis-related markers was also constructed to predict the prognosis of CRC individuals, TME and the response to immunotherapy. In addition, our transcriptome cohort of 15 paired CRC tissue, tissue-array, and various assays in 4 kinds of CRC cell lines in vitro were applied for verification. RESULTS: Cuproptosis-related markers were closely associated with both clinical prognosis and molecular functions. And the cuproptosis-related molecular phenotypes and scoring system (CuproScore) could distinguish and predict the prognosis of CRC patients, TME, and the response to immunotherapy in both public and our transcriptome cohorts. Besides, the expression, function and clinical significance of these markers were also checked and analyzed in CRC cell lines and CRC tissues in our own cohorts. CONCLUSIONS: In conclusion, we indicated that cuproptosis and CPRMs played a significant role in CRC progression and in modeling the TME. Inducing cuproptosis may be a useful tool for tumor therapy in the future.