Identification and analysis of immune-related subtypes of hepatocellular carcinoma.

Hepatocellular carcinoma is a malignance that remains difficult to cure. Immunotherapy has shown its potential application in a variety of refractory malignancies. Due to the complexity of immune microenvironment of hepatocellular carcinoma, the efficacy of immunotherapy for hepatocellular carcinoma is not as effective as expected. Expression data of hepatocellular carcinoma from the TCGA and ICGC databases were used for classification and verification of hepatocellular carcinoma subtypes. The immune-related functions and pathways were identified via gene set enrichment analysis, while the sections denoting the subsets of the immune cells were estimated using the CIBERSORT algorithm. Immunity low (Immunity_L), immunity medium (Immunity_M), and immunity high (Immunity_H) were specified as the three immune-related subtypes of hepatocellular carcinoma. The quantity of stromal and immune cells was the most substantial in Immunity_H, compared to the other subtypes. Interestingly, the proportion of M0 macrophages decreased from Immunity_L to Immunity_H, while the proportion of CD8 T cells increased. Furthermore, the HLA genes expression levels, as well as those of six immune checkpoint genes were substantially lower in Immunity_L than in Immunity_H. Functional analysis was performed for 1512 differentially expressed genes between Immunity_L and Immunity_H. Finally, the PPI network was constructed with 118 nodes. The highest connectivity degree nodes were B2M, HLA-DRA, and HLA-DRB1. The above results were verified in ICGC-JP and ICGC-FR databases with a consistent trend. In this study, we divided hepatocellular carcinoma into three subtypes and explored the immune-related characteristics of these subtypes. These results may provide new insights for immunotherapy of hepatocellular carcinoma.