Construction of a Novel Oxidative Stress Response-Related Gene Signature for Predicting the Prognosis and Therapeutic Responses in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor outcomes, and the assessment of its prognosis as well as its response to therapy is still challenging. In this study, we aimed to construct an oxidative stress response–related genes–(OSRGs–) based gene signature for predicting prognosis and estimating treatment response in patients with HCC. We integrated the transcriptomic data and clinicopathological information of HCC patients from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. LASSO Cox regression analysis was utilized to establish an integrated multigene signature in the TCGA cohort, and its prediction performance was validated in the ICGC cohort. The CIBERSORT algorithm was employed to evaluate immune cell infiltration. The response rate to immune checkpoint inhibition (ICI) therapy was assessed using a TIDE platform. Drug activity data from the Cancer Genome Project and NCI-60 human cancer cell lines were used to predict sensitivity to chemotherapy. We successfully established a gene signature comprising G6PD, MT3, CBX2, CDKN2B, CCNA2, MAPT, EZH2, and SLC7A11. The risk score of each patient, which was determined by the multigene signature, was identified as an independent prognostic marker. The immune cell infiltration patterns, response rates to ICI therapy, and the estimated sensitivity of 89 chemotherapeutic drugs were associated with risk scores. Individual prognostic genes were also associated with susceptibility to various FDA-approved drugs. Our study indicates that a comprehensive transcriptomic analysis of OSRGs can provide a reliable molecular model to predict prognosis and therapeutic response in patients with HCC.