Diosgenin targets ITGA11-driven angiogenesis in hepatocellular carcinoma: Prognostic and mechanistic insights

LIHC is a solid tumor with poor prognosis. Angiogenesis-related gene models have been developed for diseases such as cutaneous melanoma and cervical cancer to accurately predict prognosis, but angiogenesis models for LIHC have not been reported. The goal of our work is to develop a new angiogenic prognostic model for LIHC.

Based on TCGA data, we constructed a 10 gene-model of angiogenesis-related genes using WGCNA and LASSO regression algorithm. We also evaluated its prognostic significance using the ROC curve and the K-M survival analysis. We focused on the model gene ITGA11, examining its expression, correlation with clinicopathological features and survival, and its functional role. In vivo tumorigenesis studies, tube formation tests, and CCK8 were used to assess the pharmacological effects.

We constructed a 10-gene model based on angiogenesis-related genes in LIHC and identified ITGA11 as a key gene. ROC curve analysis showed that the model had a moderate predictive performance, with AUC values of 0.527, 0.486, and 0.571 for 1-, 3-, and 5-year overall survival. Survival analysis confirmed that high ITGA11 expression was significantly associated with poor prognosis (HR = 1.48, 95 % CI: 1.04-2.12, p = 0.03). Functionally, ITGA11 was highly overexpressed in LIHC and promoted angiogenesis-related invasion and migration. Overexpression of ITGA11 increased the expression of VEGFA, thereby stimulating angiogenesis. Conversely, diosgenin treatment markedly downregulated ITGA11, VEGFA, and CCL11 expression in LIHC cells, leading to the suppression of angiogenesis both in vitro and in vivo.

We developed a predictive model for vascular issues in LIHC, identified important gene ITGA11 that can promote angiogenesis in LIHC and influence tumor progression in LIHC patients through the regulation of angiogenesis. We also found a small molecule medication called diosgenin that can target ITGA11's angiogenic effects.