| Objective: Hepatocellular carcinoma(HCC)is the most common histological type of tumor in liver cancer.The early symptoms are not typical.the disease is usually in the middle and late stage when patients show obvious symptoms,and the prognosis is not ideal,which is the difficulty and hotspot of current research.Statistical analysis showed that hepatitis B virus was the most important independent risk factor for hepatocellular carcinoma,and more than half of liver cancer cases had been infected with hepatitis.In order to find more treatment options,we used the public gene chip database and bioinformatics analysis to screen key genes related to the transformation of hepatitis B into hepatocellular carcinoma,explore their expression and prognosis,and predict the potential role of traditional Chinese medicine in the prevention and treatment of hepatocellular carcinoma.Methods: 1.In this study,the expression profiles of GSE83148,GSE62232 and GSE84402 chips were downloaded from Gene expression omnibus database.GEO2 R was used to analyze differentially expressed genes(DEGs)in normal liver tissue,hepatitis B tissue,and hepatocellular carcinoma.The obtained DEGs were analyzed for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment.2.STRING11.5 was used to construct the protein-protein interaction network(PPI),and the top 15 genes with node values in the network were selected again by Cytoscape3.9.1 software as key genes in this study.3.GEPIA database was used to verify The Overall Survival(OS)of key genes in HCC samples of The Cancer Genome Atlas(TCGA)database,excluding DEGs without statistical significance.The key genes involved in the transformation of hepatitis B to hepatocellular carcinoma were obtained.4.To study the relationship between key transformation genes and immune cell infiltration in tumor microenvironment,and analyze the correlation between key genes and key genes.5.The obtained key genes were imported into Coremine Medical database to screen Chinese medicines that have potential therapeutic effects.The active ingredients and target information of Chinese medicines were obtained from TCMSP and SWISS predication database.The network diagram of“TCM-Component-target” was constructed using cytoscape,and key targets involved in regulation were calculated according to the network node values.Results: 1.A total of 64 related DEGs were screened out in this study(P < 0.05).KEGG analysis showed that DEGs mainly induced cell cycle,interaction between viral proteins and cytokines,and TNF signaling pathway,etc.GO analysis showed that DEGs mainly regulated cell division,cell cycle,inflammatory response,extracellular structure,protein binding and other functions.2.PPI network analysis and Cyto Hubba plug-in screened the top 15 genes.3.A total of 14 key genes related to transformation were screened out through GEPIA database,which were BUB1 B,DLGAP5,MCM6,PRC1,KIF20 A,ZWINT,TTK,PBK,TPX2,CCNE2,NEK2,MCM10,PTTG1,RAD51AP1.Survival analysis indicated that high expression of these 14 genes was significantly associated with decreased overall survival of patients with hepatocellular carcinoma(P < 0.05).4.Correlation studies showed that the expression of these 14 key genes was positively correlated with the immune infiltration of CD4+T cells,CD8+T cells and macrophages in tumor microenvironment.5.Through Coremine Medical and TCMSP database,Five potential herbal medicines were predicted by Coremine Medical and TCMSP databases to interfere with the hepatitis B-hepatocellular carcinoma transformation process,namely artemisia annua L,citri fructus,anemarrhenae rhizoma,aurantii fructus and aurantii fructus immaturus,which are mainly involved in the hepatocellular hepatitis-carcinoma transformation process mainly by regulating the AKT1,MYC,MAPK3,RAF1,P53 and HARS targets.Conclusion: Using bioinformatics analysis,14 key genes related to the transformation of hepatitis B to hepatocellular carcinoma were identified,and all of these genes were correlated with overall survival in hepatocellular carcinoma.Based on the key genes,we screened out the potential effective traditional Chinese medicines for preventing and treating the transformation of viral hepatitis B to hepatocellular carcinoma,which were artemisia annua L,citri fructus,anemarrhenae rhizoma,aurantii fructus and aurantii fructus immaturus,respectively,the main targets of the active components of traditional Chinese medicines were revealed through network pharmacology. |
