Evaluating the Impact of Cuproptosis-Related Genes on Prognosis and the Tumor Microenvironment in Colon Cancer

Abstract

Design: Cuproptosis, a novel copper-induced cell death mechanism dependent on mitochondrial respiration, has been identified. Despite its implications, the roles of cuproptosis-related genes in the prognosis and tumor microenvironment of colon cancer remain largely unexplored. This study aims to elucidate the prognostic and microenvironmental impacts of cuproptosis-related genes in colon cancer through comprehensive genetic and transcriptional analysis. Methods From four independent databases of TCGA and GEO datasets, we characterized the set of cuproptosis-related genes in 1124 colon cancer samples from the fields of genetics and transcription, and then evaluated their expression patterns. We identified two CRGclusters, and found that distinguishing clinicopathological features, prognosis, and tumor microenvironment cell infiltration characteristics were correlated with cuproptosis-related genes expression. Moreover, a predive risk score for overall-survival was established and its predictive capability in colon cancer patients was validated by Kaplan-Meier analysis, and receiver operating characteristic curves. Subsequently, a nomogram was constructed to improve the clinical features of the risk cores. Results The two cuproptosis-related gene clusters exhibited distinct clinicopathological and prognostic profiles, with significant variations in tumor microenvironment cell infiltration. High-risk scores were associated with increased mutation burdens, high microsatellite instability, and elevated immune cell infiltration, suggesting enhanced responsiveness to immunotherapy. The nomogram demonstrated robust predictive capabilities, enhancing the prognostic assessments in clinical settings. Conclusion Our findings not only deepen the understanding of cuproptosis-related genes in colon cancer but also pave the way for new prognostic tools and more effective immunotherapeutic strategies, leveraging the unique aspects of the cuproptosis pathway.