Cuproplasia characterization in colon cancer assists to predict prognosis and immunotherapeutic response.

Introduction: Colon cancer is the 3 most prevalent cancer worldwide, with more than 900,000 deaths annually. Chemotherapy, targeted treatment, and immunotherapeutic treatment are the three cornerstones of colon cancer treatment; however, the occurrence of immune therapy resistance is the most pressing problem to solve. Copper is a mineral nutrient that is both beneficial and potentially toxic to cells and is increasingly implicated in cell proliferation and death pathways. Cuproplasia is characterized by copper-dependent cell growth and proliferation. This term encompasses both neoplasia and hyperplasia and describes the primary and secondary effects of copper. The connection between copper and cancer has been noted for decades. However, the relationship between cuproplasia and colon cancer prognosis remains unclear.

Method: In this study, we applied bioinformatics approaches including WGCNA, GSEA and etc. to delineate cuproplasia characterization of colon cancer, set up a robust Cu_riskScore model based on cuproplasia-relevant genes and found its relevant biological processes use qRT-pCR to validate our results on our cohort.

Result: The Cu_riskScore is found to be relevant to Stage and MSI-H subtype, and some biological processes including MYOGENESIS and MYC TARGETS. The Cu_riskScore high and low groups also showed different immune infiltration pattern and genomic traits. Finally, the result of our cohort showed the Cu_riskScore gene RNF113A has a marked effect in predicting immunotherapy response.

Discussion: In conclusion, we identified a cuproplasia-related gene expression signature consisting of six genes and studied the landscape of the clinical and biological characterization of this model in Colon Cancer. Furthermore, the Cu_riskScore was demonstrated to be a robust prognostic indicator and predictive factor for the benefits of immunotherapy.