The role of a cuproptosis-related prognostic signature in colon cancer tumor microenvironment and immune responses

Background: Colon adenocarcinoma (COAD) is a common malignant tumor of the digestive tract with poor clinical outcomes. Cuproptosis is a novel cell death mechanism and linked to mitochondrial respiration. However, the role of cuproptosis in colon cancer tumor microenvironment (TME) and immune responses remains unknown. Methods: We conducted difference analysis to identify the differential expressed cuproptosis-related genes (CRGs). According to the CRGs, the TCGA-COAD samples were categorized using consensus clustering. The LASSO regression analysis was utilized to develop the cuproptosis-related signature. We then verified the model reliability by Kaplan-Meier, PCA, and ROC analysis. The GES39582 cohort served as the validation set. GO and KEGG functional analyses were conducted to investigate the underlying mechanism. We compared the infiltration levels of immune cells, the expression levels of immune checkpoints, and microsatellite instability (MSI) status between the high- and low-risk groups. Additionally, the relationships between the risk signature and immune cells and cancer stem cell (CSC) were analyzed. Results: Finally, we identified 9 differentially expressed CRGs in COAD. According to the expression of CRGs, the TCGA-COAD samples were separated into two clusters. The 11-gene signature was established by LASSO, and it had excellent predictive power for COAD prognosis. Besides, we used the GSE39582 cohort to validate the prognostic value of the model. GO and KEGG results demonstrated that the survival differences between two risk groups was mainly linked to the extracellular matrix (ECM). Further immune characterization analysis showed the significant differences in the immune cell infiltration and immune responses between two risk groups. Conclusion: Overall, the novel cuproptosis-related signature was able to accurately predict COAD prognosis and played important roles in COAD tumor microenvironment and immune responses.