Prognostic Values of Immune Scores and Immune Microenvironment-Related Genes for Hepatocellular Carcinoma

Abstract

Background: Immunotherapy, as a very promising treatment, has the potential to change the therapeutic landscape for malignancies. However, due to the complexity of immunotherapy and the heterogeneity of Hepatocellular carcinoma (HCC), it is crucial to grasp the characteristics of the tumour immune microenvironment to improve effects of immunotherapy. Methods: The ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm was used to calculate the immune and stromal scores for quantitative analysis of immune and stromal cell infiltration in HCC. The weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were analysed to identify immune microenvironment-related genes. Findings: Immune and stromal scores calculated by ESTIMATE closely represented immune cell components in the tumour microenvironment. Patients with high immune scores had a higher 4-year survival rate. TP53, CTNNB1, and AXIN1 mutations significantly varied with immune scores. In immune score-related modules analysis, Kyoto encyclopaedia of genes and genomes (KEGG) pathways and gene ontology (GO) terms were closely related to immune processes, tumorigenesis, and metastasis. Twelve new immune microenvironment-related genes were identified and had significantly positive correlations with seven checkpoint genes. In prognostic analysis, eleven immune microenvironment-related genes exhibited high expression, nine of which were validated in the GSE62232 dataset and were significantly associated with a good prognosis (P<0.05). Interpretation: Calculating immune score and stromal score could help to determine tumour purity and immune cell infiltration in the tumour microenvironment. Nine immune microenvironment-related genes identified in this study had potential as prognostic markers for HCC. Funding Statement: This research received no external funding. Declaration of Interests: The authors have declared that no conflict of interest exists Ethics Approval Statement: The data from TCGA, GEO and The Human Protein Atlas were all publicly available and open access, so no approval was needed from the ethics committees.