Bioinformatic Analysis of Key Genes Related to Tumor Microenvironment in Hepatocellular Carcinoma

Abstract

Background: Tumor microenvironment (TME) plays important roles in the development of different types of cancer. However, the critical regulatory members of TME related to hepatocellular carcinoma (HCC) remain unclear. In this study, a bioinformatic analysis based on Cancer Genome Atlas (TCGA) and Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) datasets was conducted to predict the key genes affecting TME in HCC.Material and Methods: First, 340 patients and 20531 genes’ expression data with ESTIMATE scores were filtered and combined to identify differentially expressed genes. Next, protein-protein interaction (PPI) network and functional enrichment analysis were conducted to find hub genes. Then, log-rank test and functional enrichment analysis were conducted on the consensus genes and hub genes. Finally, Kaplan-Meier curves of the hub genes were drawn. As verification, those genes were searched on Oncomine database.Results: Among all differentially expressed genes, 916 genes were expressed in both the immune and stromal groups. The Gene Ontology (GO) terms they enriched were T cell activation, leukocyte migration, collagen-containing matrix, external side of plasma membrane, receptor ligand and activator activity. Cytokine-cytokine receptor interaction was the most significant Kyoto Encyclopedia of Genes and Genomes (KEGG) term. Furthermore, cd3e, cd3g, hla-dpa1, hla-dpb1, lck, and map4k1 hub genes were low expressed in 304 patients, participating in a variety of responses including immune response−activating cell surface receptor signaling, immune response−activating signal transduction, clathrin−coated vesicle membrane, immune receptor activity， peptide binding and amide binding pathways. Their low expression was also verified on Oncomine database.Conclusion: cd3e, cd3g, hla-dpa1, hla-dpb1, lck, and map4k1 participated in many aspects related to TME, and their low expression constructs a signature, may predict a poor 5 years’ survival in hepatocellular carcinoma.