Integrative Characterization of Immune-relevant Genes in Hepatocellular Carcinoma
Wei-Feng Hong, Yujun Gu, Na Wang, Jie Xia, Hengyu Zhou, Ke Zhan, Ming-Xiang Cheng, Ying Cai
Abstract
BACKGROUND AND AIMS: Tumor microenvironment plays an essential role in cancer development and progression. Cancer immunotherapy has become a promising approach for the treatment of hepatocellular carcinoma (HCC). We aimed to analyze the HCC immune microenvironment characteristics to identify immune-related genetic changes. METHODS: Key immune-relevant genes (KIRGs) were obtained through integrating the differentially expressed genes of The Cancer Genome Atlas, immune genes from the Immunology Database and Analysis Portal, and immune differentially expressed genes determined by single-sample gene set enrichment analysis scores. Cox regression analysis was performed to mine therapeutic target genes. A regulatory network based on KIRGs, transcription factors, and immune-related long non-coding RNAs (IRLncRNAs) was also generated. The outcomes of risk score model were validated in a testing cohort and in clinical samples using tissue immunohistochemistry staining. Correlation analysis between risk score and immune checkpoint genes and immune cell infiltration were investigated. RESULTS: were closely related to the risk score, and CD4 T cells, macrophages, and neutrophils were the primary immune infiltration cell types. CONCLUSIONS: Our results highlight the importance of immune genes in the HCC microenvironment and further unravel the underlying molecular mechanisms in the development of HCC.