Development of a cuproptosis-related prognostic signature and associated regulatory axis in colon cancer

Abstract

OBJECTIVES: Based on the TCGA and GEO databases, we constructed a cuproptosis-related gene signature to predict colon cancer prognosis. Furthermore, we explored the role of cuproptosis regulators in the development of colon cancer. METHODS: In the discovery set from the TCGA-COAD cohort (n = 452), cuproptosis regulators were incorporated in a LASSO-COX regression to construct our signature. The predictive ability was validated in the GEO cohort (n = 562). Subsequently, the immune microenvironment was compared between high- and low-risk groups according to risk score. The role of FDX1 during colon cancer was also investigated. RESULTS: A four-gene signature was successfully constructed. This signature could discriminate colon cancer with different prognoses both in the discovery (P < 0.001) and validation sets (P = 0.015). Immune infiltration analysis revealed that tumors in the high-risk group had more infiltrated CD8⁺ T and activated NK cells (both P < 0.001), while low-risk tumors had more infiltrated CD4⁺ T (P < 0.001) and plasma cells (P < 0.01). Moreover, the hsa-miR-9-3p/FDX1 pathway was found in colon cancer. CONCLUSION: We constructed a cuproptosis-related gene signature in colon cancer; its performance was robust in the discovery and validation cohorts. The relationship between FDX1 and tumorigenesis in colon cancer was also elucidated.