Exploring potential targets of Actinidia Chinensis Planch root against hepatocellular carcinoma based on network pharmacology and molecular docking and development and verification of immune-associated prognosis features for hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the malignant tumors with the highest morbidity and mortality worldwide, and its prognosis remains a challenge. Actinidia chinensis Planch (ACP) root has good efficacy against HCC. This study aimed to explore the link between ACP and potential targets of HCC, and to develop a novel immune-based gene signature to predict HCC patient survival.Methods: Transcriptome data and clinical information on HCC were obtained from The Cancer Genome Atlas (TCGA; HCC: 374, normal: 50) and International Cancer Genome Consortium (ICGC) database (HCC: 243, normal: 202). Combined with the 2,483 immune-related genes from the Immport database, we used the least absolute shrinkage and selection operator (LASSO) to construct a prognostic model. Patients were divided into high-risk and low-risk groups by the median of the risk scores of the TCGA cohort. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were used to estimate the predictability of the model in HCC prognosis, and carried out external validation based on ICGC cohort. We analyzed the correlation of this model with immune cells and immune checkpoint genes. Finally, molecular docking of these genes and the corresponding ACP components. Results:We constructed a prognostic model composed of 3 immune-related genes [epidermal growth factor (EGF), baculoviral inhibitor of apoptosis repeat-containing protein 5 (BIRC5), and secreted phosphoprotein 1 (SPP1)]. And the high-risk group had a lower overall survival (OS) rate compared to the low-risk group (TCGA cohort: P=1.761e-05, ICGC cohort: P=8.716e-04). The outcomes of the AUC of ROC of prognostic risk model to predict for 1-, 2-, and 3-year OS: TCGA cohort: 0.749, 0.710, and 0.653 and ICGC cohort: 0.698, 0.736, and 0.753. Molecular docking results showed that quercetin had good binding activities with SPP1, BIRC5, and EGF, and ursolic acid (UA) and BIRC5 also had this feature.Conclusions: Our study speculates that ACP root anti-HCC may be involved in the immune regulation of the body by targeting EGF, BIRC5 and SPP1, which possess great potential and value as early warning molecules for HCC. This model may provide a reference for individualized diagnosis and treatment for HCC patients.

Progress of Actinidia chinensis Planch. root extract (acRoots) in cancer immunity

“…59 Meilin Qu et al constructed a prognostic model of the extract of acRoots in hepatocellular carcinoma composed of 3 immune-related genes, epidermal growth factor, baculoviral IAP repeat containing 5 (BIRC5), and secreted phos-phoprotein 1 (SPP1). 60 BIRC5 was highly associated with CD8 + T cells and promoted PD-ligand 1 (PD-L1) levels in lung cancer cell A549 but exerted opposite effects in NCI-H1299 cells, which lack p53 expression. 61 These results were consistent with our previous study of the acRoots on lung cancer proliferation and gene expression.…”