Identification of Key Drug Targets and Molecular Mechanisms of Curcumae Rhizoma Acting on HBV-Related HCC: Weighted Correlation Network and Network Pharmacological Analyses.

Abstract

Background Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has poor prognosis and high mortality rate. Curcumae Rhizoma, a classic Chinese medicinal herb, is often used to treat tumors. Methods Active ingredients of Curcumae Rhizoma were extracted from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database, and potential targets were predicted by the TCMSP database and Swiss Target Prediction database. The key drug targets were filtered by intersecting predicted targets, DEGs, and genes in important modules from WGCNA. Besides, the key drug targets were used to construct a network of “herb-active ingredient-target-disease” interactions and subjected to enrichment analysis and protein-protein interaction (PPI) analysis. The hub targets based on PPI analysis was evaluated by the KMplotter database. Results Three active ingredients of Curcumae Rhizoma were collected with OB ≥ 30% and DL ≥ 0.18, including hederagenin, wenjine, and bisdemethoxycurcumin. The key drug targets were mainly enriched in cell cycle checkpoint, DNA integrity checkpoint, and peptidyl-serine modification. Besides, Curcumae Rhizoma treatment of HBV-related HCC mainly involved the p53 signaling pathway and arachidonic acid metabolism. Finally, ESR1 and PTGS2 were identified as hub targets from PPI analysis. ESR1 was found to be correlated with survival in liver cancer patients with hepatitis. Conclusion Based on WGCNA and network pharmacological analysis, our results illustrated that Curcumae Rhizoma might work through regulating multitargets and multipathways in HBV-related HCC.