An immune-related biomarker index for predicting the effectiveness of immunotherapy and prognosis in hepatocellular carcinoma.

Objective: Currently, there are no recognized biomarkers for predicting the immunotherapy response and prognosis of hepatocellular carcinoma (HCC). This study aimed to establish an immune-related gene prognostic index (IRGPI) for HCC, and to investigate the clinical, immune, molecular, and microenvironmental characteristics of the IRGPI subgroups, as well as their impact on the effectiveness of immune checkpoint inhibitors (ICIs) therapy and patients' prognosis.

Methods: We analyzed the LIHC dataset (n = 424) from the The Cancer Genome Atlas (TCGA) database and the GSE10140 dataset (n = 84) from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA) and univariate/multivariate Cox regression analysis to identify immune-related hub genes with prognostic significance. Subsequently, The IRGPI was then established with these special genes obtained, and the molecular, immune, and clinicopathological characteristics of the IRGPI subgroups, along with their predictive role in ICIs treatment and HCC prognosis, were investigated.

Results: The IRGPI was composed of nine genes, namely CHGA, GAL, CCR3, MMP7, STC1, UCN, OXT, SOCS2, and GCG. The IRGPI-high group exhibited a worse prognosis in both the TCGA and GEO databases compared to the IRGPI-low group. The IRGPI-high group was primarily associated with adaptive immune response and cell-cell interaction pathways and exhibited a higher frequency of gene mutations (such as TP53 and CTNNB1), higher expression of PD-L1 and CTLA4, a higher proportion of macrophages M0 and follicular helper T cells, and a higher APC_co_inhibition and T_cell_co-inhibition immune score. Furthermore, the IRGPI-high group was associated with worse immune subtypes, clinicopathological characteristics, immunotherapy response, and clinical prognosis.

Conclusion: IRGPI is a biomarker with significant potential for predicting the immunotherapy response and prognosis of HCC patients, and is closely related to the immunosuppressive microenvironment and poorer clinicopathological characteristics.