Functional characterization of angiogenesis genes in hepatocellular carcinoma via integrated bulk and single cell RNA sequencing

Hepatocellular carcinoma (HCC) originates from hepatocytes and accounts for over 80% of primary liver cancers. Despite numerous studies have explained the role of certain angiogenesis-related and integrated stress response related genes in the development of HCC, few studies have explored the function of all angiogenesis-related and ISR(Integrated stress response)-related genes, as well as their applications in therapeutic prediction models. Here, by integrating bulk and single cell transcriptome data, We first explored the expression patterns of genes at the intersection of angiogenesis and the integrated stress response (ISR). To comprehensively identify angiogenesis-related gene modules, we then performed WGCNA (weighted gene co-expression network analysis) using a broader angiogenesis gene set, revealing modules strongly correlated with angiogenic activity.Based on these core genes, we constructed a prognostic model to evaluate patient outcomes and responses to immunotherapy, which is valuable for informing treatment options. Furthermore, through drug response modeling, we identified several drugs targeting angiogenesis genes that could serve as potential therapeutic options. Single-cell transcriptome analysis also revealed that DAB2, which is highly expressed in APOA2+ macrophages, may be involved in the cellular response to signals from fibroblast cells via the THY1 pathway. Finally, molecular docking studies indicated that dihydroergotamine might be a promising candidate drug for targeting DAB2. This study systematically investigated the expression changes of angiogenesis genes in HCC, constructed a tumor prognosis prediction model, and explored potential therapeutic targets and drugs. These findings are of significance for guiding the selection of treatment options and identifying therapeutic targets for HCC.