Hypoxia-Related Immune Gene Signature Predicting Prognosis in Patients With Hepatocellular Carcinoma

Abstract

BackgroundHepatocellular carcinoma (HCC) remains a global health challenge. Increasing evidence indicates that hypoxia is crucial in the evolution and progression of HCC by regulating the tumor immune microenvironment. The present study aimed to construct a prognostic relevant hypoxia-related immune gene (HRIG) signature. MethodsWe analyzed the expression profile of the 163 HRIGs and clinical information of 371 patients with HCC obtained from The Cancer Genome Atlas (TCGA). Then, consensus clustering analysis was performed to divide HCC patients into clusters 1 and 2 based on the HRIG expression. Subsequently, A multigene signature was constructed by Least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Then, we evaluated the prognostic capability of this signature by Kaplan-Meier analysis, univariate Cox regression and multivariate Cox regression. The prognostic value of the signature was validated in the International Cancer Genome Consortium (ICGC) database. Furthermore, the functional enrichment analyses were preformed to elucidate their biological significance. Finally, we evaluated the infiltration of immune cells and the sensitivity of administrating chemotherapeutic agents.ResultsA total of 37 prognosis-related HRIGs were obtained. Subsequently, we constructed an 8-gene signature on the basis of prognosis-related HRIGs, which had a good performance in predicting the overall survival of patients with HCC. In addition, the signature expressed robust when validated in ICGC. The results revealed that these genes involved in some of the HCC-related pathways and was associated with the infiltration of immune cell subtypes. More importantly, the identified model was linked to the sensitivity of some chemotherapeutic agents. ConclusionsHRIG signature is an effective predictor for the prognosis of patients with HCC.