Immune classifier-based signatures provide good prognostic stratification and predict the clinical benefits of immune-based therapies for hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is an aggressive cancer with a high rate of death globally. The use of bioinformatics may help to identify immune cell-related genes both as targets for potential immunotherapies and for their value associated with predicting therapy responses. Methods: In this study, mRNA expression profiles of HCC samples from The Cancer Genome Atlas (TCGA) database were subjected to gene enrichment, cell type abundance, immune cell infiltration, and pathway enrichment analyses to determine immune cell gene features, cell type abundance, and functional annotation characteristics. We also evaluated their prognostic values using Cox regression and Kaplan–Meier analyses and assessed potential responses to chemotherapy. Four subgroups (Groups 1–4) were identified. Group 4 was associated with advanced clinical characteristics, high immune cell enrichment scores, and the poorest outcomes. Results: Differentially expressed genes (DEGs) in the HCC samples were enriched in the following pathways: antigen binding, cell surface receptor signal transduction of the immune response, and cell surface activated receptor signal transduction of the immune response. Highly expressed genes in Group 4 were enriched in elements of the WNT signalling pathway. We identified five immune-related genes (SEMA3A, TNFRSF11B, GUCA2A, SAA1, and CALCR) that were significantly related to HCC prognosis. A prognostic model based on these five genes exhibited good predictive value, with 1-year and 5-year area under the curve (AUC) values of > 0.66. Group 4 was also potentially more sensitive to EHT 1864, FH535, and lapatinib chemotherapies than the other groups. Conclusions: We identified and validated four HCC subgroups based on immune system-related genes and identified five genes that may be used for an immune-based prognostic model for HCC treatment.