Molecular mechanism of Aidi injection in treatment of hepatocellular carcinoma based on weighted gene co-expression network analysis combined with network pharmacology
Objective To investigate the molecular mechanism of Aidi injection in the treatment of hepatocellular carcinoma based on weighted gene co-expression network analysis(WGCNA),network pharmacology and molecular docking.Methods Protein expression data of hepatocellular carcinoma tissue samples and normal tissue samples were downloaded from The Cancer Genome Atlas(TCGA)database,and reducted into matrix to construct a co-expression network by WGCNA.Then genes with similar expression in tumor tissues were assigned to the same gene module,and the correlation between gene modules and tumor tissues was investigated to identify the gene module with the strongest correlation with cancer.Key modules related to hepatocellular carcinoma were screened for WGCNA analysis.The possible targets of main chemical components of Aidi injection were screened by TCM System Pharmacology Technology Platform(TCMSP),PubChem and information retrieval.The target gene corresponding to the active component of Aidi injection was matched with the hub gene in the key module to obtain the possible key target of Aidi injection against hepatocellular carcinoma.STRING database and Cytoscape software were used to construct protein protein interaction(PPI)network,and the network topology parameters were analyzed to screen the key targets.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze biological functions of key targets,and AutoDock Vina software was used for molecular docking verification.The relationship between key genes and prognosis of patients with hepatocellular carcinoma was analyzed by KM Plotter.Results A total of 378 samples and 3 775 genes were selected for WGCNA analysis.A total of 131 potential anti-hepatocellular carcinoma targets of Aidi injection were screened.The core targets of Aidi injection in the treatment of hepatocellular carcinoma were estrogen receptor 1(ESR1),baculovirus-containing IAP repeat protein 5(BIRC5),cyclin A2(CCNA2),and cell cycle checkpoint kinase(CHEK1).The potential regulatory pathways included tumor pathway,neuroactive ligand-receptor interaction,and cGMP-PKG signaling pathway.The results of molecular docking showed that the main components of Aidi injection had strong binding activity with the core targets.The high expressions of BIRC5,CCNA2,and CHEK1 and low expression of ESR1 might be correlated with the poor prognosis of patients with liver cancer.Conclusion Aidi injection can exert anti-hepatocellular carcinoma effect through multi-target and multi-pathway.
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