Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of hepatocellular carcinoma (HCC)

Growing evidence supports that the tumor microenvironment plays a key role in the development and progression of tumors. But immune microenvironment of hepatocellular carcinoma (HCC) has not yet been fully explored. In the present investigation, the clinical value and prognostic significance of immune-related genes in HCC were investigated. The immune and stromal scores of HCC were calculated through the application of Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Algorithm based on the Cancer Genome Atlas database. Differentially expressed genes were identified using the “edgeR” package of the R software. Functional annotation and pathway enrichment were performed using “ggplots2” and “clusterProfiler” packages in R software. Protein-protein interaction network was constructed using STRING, and the hub genes were identified through the Cytoscape. Survival analysis was performed using Kaplan-Meier methods. Tumor Immune Estimation Resource algorithm was used to view the immune landscape of the microenvironment in HCC. Firstly, the immune and stromal scores of HCC were calculated and we found that the immune and stromal scores of HCC were closely related to the patients’ prognosis. Then the differentially expressed genes were identified respectively stratified by the median value of the immune and stromal scores, and the immune-related genes that related to the prognosis in HCC patients were further identified. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune-related biological process. In addition, dendritic cells were found to be the most abundant in the microenvironment of HCC through Tumor Immune Estimation Resource algorithm and were significantly associated with the patients’ prognosis. To robust the results, the immune-related genes were validated in an independent dataset from the Gene Expression Omnibus database. We arrived at a more comprehensive understanding of the microenvironment of HCC and extracted 7 immune-related genes that were significantly associated with the recurrence survival of HCC.