Comprehensive Analysis of Cuproptosis-related Genes Involved in Prognosis and Tumor Microenvironment Infiltration of Colorectal Cancer

Abstract Colorectal cancer (CRC) is a common malignancy with high incidence and mortality rates. Cuproptosis, a novel form of copper-induced programmed cell death, contributes to tumor progression. Whether cuproptosis-related genes (CRGs) play a role in CRC remains unclear. Here, we systematically assessed CRG mutations in CRC. The expression of eight of the 10 CRGs was significantly different between CRC and normal tissues. CDKN2A and DLAT were identified as independent risk factors for predicting overall survival (OS) in CRC using univariate and multivariate Cox analyses, and a risk score model was constructed based on CDKN2A and DLAT. Patients with CRC were categorized into high- and low-risk groups based on their median risk scores, with those in the low-risk group having longer OS than those in the high-risk group. Receiver operating characteristic curve analysis indicated that the risk score model had good predictive accuracy for OS. Analysis of the TISCH and TISIDB database showed that CDKN2A and DLAT were associated with the TME, and the molecular subtypes and immune subtypes differed between CDKN2A and DLAT. Spearman’s analysis showed that CDKN2A and DLAT expressions were significantly associated with immune cell infiltration in CRC. Our research revealed CRGs’ prognostic value, particularly CDKN2A and DLAT, in CRC and demonstrated the relationship between CDKN2A/DLAT and immune infiltration in CRC, thereby contributing to the outcome evaluation of patients with CRC and identifying novel targets for CRC immunotherapy.