Identification of Gene Signature-Related Oxidative Stress for Predicting Prognosis of Colorectal Cancer

Abstract

Background. Colorectal cancer (CRC) is the third most common cancer. Nearly a decade of studies had shown that cancer regimens tailored to molecular and pathological features lead to improved overall survival. Oxidative stress (OS) refers to a state in which oxidation and antioxidant effects are unbalanced in the body. However, the molecular mechanism of OS-related CRC remains unclear. Methods. Univariate Cox regression analysis gained OS signature genes related to CRC prognosis, and then, different CRC molecular subtypes were obtained by consensus clustering analysis. Differential expression analysis and least absolute shrinkage and selection operator (LASSO) algorithm were used to obtain prognostic-related signature genes. Significantly, risk score was calculated by $\text{RiskScore}=\Sigma \beta i\times \text{Exp}i$ . Moreover, the Kaplan-Meier survival analysis, immune cell infiltration, and sensitivity to treatment regimens were performed to assess the model’s validity and adaptability. Finally, RiskScore incorporated clinicopathological features to further improve prognostic models and survival prediction. Results. 63 OS-related prognostic genes were obtained, and four distinct molecular subtypes of CRC were identified based on the expression characteristics. 230 differentially expressed genes (DEGs) between different molecular subtypes were compressed by LASSO algorithm, and finally, 6 OS-related genes were obtained. The Kaplan-Meier survival analysis indicated that the high RiskScore groups had poorer prognosis and the RiskScore model showed better predictive performance in all three other independent datasets. Moreover, immunotherapy/chemosensitivity analysis found that the low-risk group was more sensitive to different treatment options and could achieve better treatment outcomes. Conclusion. Oxidative stress-related RiskScore model built in this work has good predictive performance for CRC.