Identification and immunoprofiling of key prognostic genes in the tumor microenvironment of hepatocellular carcinoma

ABSTRACT

Tumor microenvironment (TME) is involved in the occurrence and development of hepatocellular carcinoma (HCC), and immune cells in the TME have been implicated in its progression and treatment. However, the association of genes involved in the TME with HCC prognosis remains unclear. Thus, in this study, we obtained transcriptomic and clinicopathological data of patients with HCC from The Cancer Genome Atlas to identify key genes in TME associated with HCC prognosis. Stromal and immune cell scores were calculated using the ESTIMATE method, and differentially expressed genes (DEGs) were determined. We identified 830 DEGs, which were further subjected to survival analyses and functional enrichment analysis. Next, we identified prognostic TME-associated DEGs, established a protein-protein interaction (PPI) network, and performed Cox analysis.Consequently, four key prognostic genes ( CXCL5, CXCL8, IL18RAP, and TREM2) associated with TME, were identified, in which CXCL5 and IL18RAP may be potential independent prognostic factors. Age, clinical stage, N stage, and risk score were also determined as significant prognostic variables. CIBERSORT was used to predict the constitution and relative content of the immune cells, wherein M0 macrophages were the most closely related to the key genes. In conclusion, CXCL5, CXCL8, IL18RAP, and TREM2 were associated with HCC prognosis and were important for immune cell invasion into the TME. Additionally, IL18RAP expression may contribute toward favorable prognosis in patients with HCC. Consequently, these genes may serve as potential biomarkers and immunotherapeutic targets for HCC.

Graphical abstract