Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma

SIMPLE SUMMARY: Oxidative phosphorylation (OXPHOS) plays an important role in the progression of colorectal adenocarcinoma (COAD). The aim of our study was to investigate the expression pattern of OXPHOS-related genes (ORGs), and an OXPHOS-related prognostic signature was constructed to classify COAD patients into high-risk and low-risk groups. Then, we analyzed the relationship between risk scores and tumor microenvironment, somatic mutation, and efficacy of immunotherapy and chemotherapy. Additionally, a nomogram was established by combining clinical features and risk scores, and its predictive ability was verified by receiver operating characteristics and calibration curves. Overall, the OXPHOS-related signature can be used as a reliable prognostic predictor of COAD patients. ABSTRACT: Oxidative phosphorylation (OXPHOS) is an emerging target in cancer therapy. However, the prognostic signature of OXPHOS in colorectal adenocarcinoma (COAD) remains non-existent. We comprehensively investigated the expression pattern of OXPHOS-related genes (ORGs) in COAD from public databases. Based on four ORGs, an OXPHOS-related prognostic signature was established in which COAD patients were assigned different risk scores and classified into two different risk groups. It was observed that the low-risk group had a better prognosis but lower immune activities including immune cells and immune-related function in the tumor microenvironment. Combining with relevant clinical features, a nomogram for clinical application was also established. Receiver operating characteristic (ROC) and calibration curves were constructed to demonstrate the predictive ability of this risk signature. Moreover, a higher risk score was significantly positively correlated with higher tumor mutation burden (TMB) and generally higher gene expression of immune checkpoint, N6-methyladenosine (m6A) RNA methylation regulators and mismatch repair (MMR) related proteins. The results also indicated that the high-risk group was more sensitive to immunotherapy and certain chemotherapy drugs. In conclusion, OXPHOS-related prognostic signature can be utilized to better understand the roles of ORGs and offer new perspectives for clinical prognosis and personalized treatment.