Identification of Immune-Related Markers in Hepatocellular Carcinoma Based on Gene Co-expression Network

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death throughout the world, with constant increasing morbidity and mortality. Existing studies suggest that immunotherapy is beneficial to the treatment of advanced HCC. At present, it is imperative to identify biomarkers suitable for HCC immunotherapy. In this paper, the mRNA expression data of HCC were downloaded from The Cancer Genome Atlas, and Stromal Score, Immune Score and ESTIMATE Score of each sample were calculated. Weighted gene co-expression network analysis clustered the pretreated genes into eight modules. The brown module that was remarkably associated with Immune Score was identified by module eigengene-immune trait analysis, in which genes were mainly enriched in immune-related pathways. Four hub genes (CCR5, CD53, ITGB2, and TYROBP) related to tumor immunity, were screened out by intramodular gene connectivity combined with protein-protein interaction network topology analysis. Kaplan-Meier survival analysis presented a correlation between high expression of CCR5 and CD53, and better prognoses of HCC patients. TIMER analysis revealed a positive correlation between expression of each hub gene and immune cell infiltration level, and a positive correlation between the expression of each hub gene and the expression of immunosuppressive factors CTLA4 and PDCD1. Gene set enrichment analysis displayed that there was an evident difference in the activation of cytokines and the activation of immune signal transduction-related pathways between high- and low-expression groups of each hub gene. In conclusion, this study identified four potential genetic markers associated with HCC immunity and assessed their association with HCC patient's prognosis and immune microenvironment. The study results are expected to provide theoretical guidance for immunotherapy of HCC patients.

Keywords: Hepatocellular carcinoma; Immune traits; Immunosuppressive molecules; PPI network; WGCNA.