The immune-related gene-based prognostic index predicts the prognosis and effect of immune checkpoint inhibitors in hepatocellular carcinoma

Abstract

Background: Immune-related genes have been confirmed to be related to tumor development and anti-tumor immune response. Therefore, immune-related genes are potential candidate for predicting prognosis and immunotherapy response. We aimed to explore the relationship between immune-related genes and the prognosis, tumor microenvironment and response to immunotherapy in HCC. Methods: The immune-related gene-based prognostic index (IRGPI) is constructed by 4 hub genes that are most closely related to prognosis among 1.811 immune related genes. We then sequentially compared the differences in clinical characteristics, driver gene mutations, immune microenvironment and immunotherapy between the two groups of IRGPI. Finally, multiplex immunofluorescence staining was used to assess the abundance of infiltrating CD8+ T cells in tumor microenvironment between different subgroups. Results: IRGPI-high significantly related to higher disease progression and shorter survival time. IRGPI is accompanied by a higher TMB and frequency of driver gene mutations that predicts worse prognosis. In tumor microenvironment, the number and activity of tumor-infiltrating immune cells in the IRGPI-low group was significantly greater than that of the IRGPI-high. TIDE and three immunotherapy datasets showed that patients in the IRGPI-low group are more in an immune dysfunction state and respond well to ICIs. Immunostaining on the HCC cohort further confirmed that CD8+ T cells were more abundant in IRGPI-low group, while the tumor microenvironment of IRGPI-high group presents a scene of immune desert, which corresponds to our results and partly explains why IRGPI-high group cannot respond well to ICIs. Conclusions: IRGPI was created based on the immune-related genes in HCC. The novel prognostic model can predict prognosis and response to ICIs in HCC patients.