An integrative genomic analysis of angiogenesis in hepatocellular carcinoma: from canonical drivers to emerging biomarkers.

Angiogenesis, the production of new blood capillaries from pre-existing vasculature, is an important mechanism necessary for cancer progression and metastasis. This process may be regulated by the balance of pro-angiogenic and anti-angiogenic factors. The disruption of this balance leads to the induction of angiogenesis. Thus, there is a high necessity to identify these angiogenesis-related genes. In this study, we have used GeneCards database to obtain a list of angiogenesis-related genes followed by construction of protein-protein interaction (PPI) network using STRING database. Out of 37 angiogenesis-related genes, a single-gene cluster containing 27 genes was identified using MCODE analysis. The top ten hub genes were identified as FGF2, HIF1A, VEGFC, VEGFA, MMP9, THBS1, MMP2, KDR, IL6, and NOS, which were further analyzed. FunRich application was used to perform gene enrichment analysis and identify top interactors by constructing an interaction map. PPI map of each individual hub gene was constructed using search tool for the retrieval of interacting genes/proteins (STRING) database. The expression levels of each individual hub gene in HCC (liver hepatocellular carcinoma-LIHC dataset) and normal tissue were analyzed using the gene expression profiling interactive analysis 2 (GEPIA2) portal. The prognostic value of the hub genes was analyzed using Kaplan-Meier survival plot. The translational-level expression was analyzed using the IHC section images from the Human Protein Atlas (HPA) database. Thus, targeting these factors for therapy, diagnosis, or prognosis could be a key strategies in the field of oncology.