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

Cancers (Basel). 2022 Sep 16;14(18):4503. doi: 10.3390/cancers14184503.

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.

Keywords: colorectal adenocarcinoma; oxidative phosphorylation; prognosis predicting; tumor microenvironment.

Grants and funding

This study was supported by Jiangsu Province Hospital of Chinese Medicine Peak Talent Program (y2021rc27).