A Novel Angiogenesis-Related Prognostic Signature Associated with the Hepatocellular Carcinoma Immune Microenvironment and Survival Outcome

PURPOSE: Hepatocellular carcinoma (HCC) is a highly vascularized solid tumor characterized by neovascularization and vascular invasion. Angiogenesis plays an essential role in the occurrence and development of liver cancer. Our study aimed to investigate the prognostic value of angiogenesis-related genes in liver cancer. PATIENTS AND METHODS: The transcriptome data and corresponding clinical information of patients with liver cancer were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. In the TCGA cohort, differential expression and prognostic analyses were used to screen angiogenesis-related candidate prognostic genes. We then used least absolute shrinkage and selection operator regression analysis to construct a prognostic signature using 10 angiogenesis-related prognostic genes. The reliability of the prognostic signature was assessed in the TCGA and ICGC cohorts. In addition, we comprehensively analyzed the correlation of the prognostic signature with the tumor microenvironment, chemotherapy drugs, and specific genes. RESULTS: We identified 37 angiogenesis-related differentially expressed genes that were remarkably associated with prognosis. Ten of these genes were used to establish a survival and prognostic signature. This signature can distinguish between high-risk and low-risk groups and performs well in overall survival prediction, as demonstrated by internal and external validations. In addition, we observed that the high-risk group was remarkably associated with immune infiltration in the tumor microenvironment and had a different sensitivity to chemotherapeutic agents compared with the low-risk group. Moreover, the high-risk population was positively correlated with the expression of several special genes, such as immune checkpoint-related genes. CONCLUSION: Our results demonstrated that prognostic signatures based on angiogenesis-related genes are involved in the development of HCC and may provide new insights into accurate clinical decision-making and therapeutic evaluation of patients with HCC.