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

Abstract

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.

Hepatocellular carcinoma pathogenesis: Epigenetics and relationship with cancer hallmarks

“…Hepatocellular carcinoma is a hyper-vascular tumor characterized by neovascularization, which plays an important role in the growth and progression of HCC (Jiang et al, 2022). A switch to an angiogenic phenotype is a prerequisite for the development from a premalignant stage to an invasive tumor.…”

Effect of novel anti-tumor and anti-angiogenesis drug taurolactone on angiogenic factor AGGF1 and angiogenesis mimicry in patients with hepatocellular carcinoma

“…Taurolactone, a novel and promising drug with potential anti-cancer and anti-angiogenic properties, has garnered significant attention. Taurine, an organic compound containing sulfur, has demonstrated anti-angiogenic and anti-tumor properties in various disease models [ 7 ]. Nevertheless, additional research and elucidation are required to fully understand the potential impact and underlying mechanisms of this treatment approach for HCC.…”

Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis

“…To date, several prognostic prediction models based on angiogenesis-related genes have been developed for HCC, but no study has investigated this key factor of HCC angiogenesis in detail. Moreover, the role of VEGF in hepatocellular carcinoma angiogenesis is not fully understood [24][25][26][27]. Moreover, considering the heterogeneity and complexity of hepatocellular carcinoma, the detection and inhibition of VEGF or VEGFR alone may not be sufficient to reflect and predict the angiogenic status and therapeutic efficacy of HCC [28].…”