Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a highly invasive disease, and advanced tumours are often accompanied by a poor prognosis; thus, the treatment of advanced HCC is still based on comprehensive treatment. Bupleurum chinensis DC. (Chaihu) is widely used in the treatment of liver cancer in traditional Chinese medicine. However, few studies have explored the mechanism of action of Chaihu in hepatocellular carcinoma or its impact on prognosis. METHODS: The core target was obtained by matching differentially expressed genes (DEGs) in HCC tissues to targets associated with Chaihu. These targets were used to identify HCC subtypes and build prognostic models for patients with HCC. We also explored the immune microenvironment and enrichment pathways between different clusters. The LASSO(The Least Absolute Shrinkage and Selection Operator) regression model was used to establish a risk-score model composed of four hub genes. The Kaplan-Meier curve showed significant differences in survival between the high- and low-risk groups. The risk-score model was then combined with clinical information to develop a nomogram to predict patient survival. Finally, three hub genes identified in the prognostic model were verified using in vitro experiments. RESULTS: We screened 77 prognostically relevant DEGs and selected four genes for the risk score model. Multivariate regression analysis revealed that the risk score model was an independent prognostic factor. The survival rate was significantly lower for the high-risk group than for the low-risk group (P < 0.05). In vitro experiments showed that the compounds present in Chaihu decreased the expression of prognostic genes. The combination of prognostic analysis and cell experiments showed that Chaihu exerted a potential therapeutic effect on hepatocellular carcinoma. CONCLUSIONS: This study established a risk-scoring model for Chaihu-related genes and evaluated its effectiveness at determining the characteristics of Chaihu that are favourable for the prognosis of liver cancer. Chaihu improved the prognosis by acting on three core prognostic genes (MMP1, NQO1, and PLK1) and the immune microenvironment, thus benefiting patients with HCC.