乙型肝炎病毒相关肝细胞癌的关键基因筛选及临床意义

Screening of Key Genes in Hepatitis B Virus Related Hepatocellular Carcinoma and Its Clinical Significance

目的应用生物信息学筛选出乙型肝炎病毒(HBV)相关肝细胞癌的关键基因及潜在药物。方法从GEO数据库下载HBV相关肝癌高通量芯片数据集GSE121248和GSE49713,通过GEO2R法分析获得差异表达基因(DEGs)。通过DAVID数据库对DEGs进行GO和KEGG分析。String数据库建立蛋白-蛋白互作网络(PPI),利用Cytoscape软件构建hub基因及可视化网络。通过Kaplan-Meier Plotter和UALCAN数据库确认有临床预后价值的关键基因。通过cBioPortal数据库分析关键基因在肝癌组织中的表达相关性、突变和生存预后,通过CTD数据库获取对关键基因有潜在作用的化合物并进行比较。结果共获得93个DEGs,这些基因主要富集在氧化还原、蛋白质水解和有丝分裂核分裂等生物学过程;主要富集在细胞外小体、细胞外区域和细胞外隙等细胞成分;主要与血红素结合、铁离子结合和染色质结合等功能;主要集中在代谢途径,丙氨酸、天冬氨酸和谷氨酸代谢以及色氨酸代谢3条通路。筛选分析hub基因并从中得到10个关键基因,在突变、表达相关性及预后上均有统计学意义(P<0.05)。基于以上靶点筛选出白藜芦醇、雷公藤甲素、穿心莲内酯、黄芩提取物、水飞蓟宾、姜黄素、槲皮素、隐丹参酮等候选药物。结论本研究通过数据挖掘与生物信息学分析,找到多个关键基因与潜在药物,为临床HBV相关肝癌治疗靶点的选择及药物方案的优化提供了参考。

Objective To screen the key genes and potential drugs of hepatocellular carcinoma(HCC)related to hepatitis B virus(HBV)using bioinformatics.Methods The High-throughput microarray datasets GSE121248 and GSE49713 of HBV related HCC were downloaded from GEO database,and the DEGs were obtained by GEO2 R analysis.The gene ontology function annotation and pathway enrichment analysis of DEGs were performed with DAVID database.The protein-protein interaction network(PPI)was established by String database,and the hub genes and their visual network were constructed by using the software of Cytoscape.Kaplan-Meier Plotter database and UALCAN database were used to identify the key genes with clinical prognostic significance.The cBioPortal database was used to analyze the co-expression,mutation and survival prognosis of key genes in HCC.Compounds with potential effects on key genes were obtained and compared through CTD database.Results The 93 DEGs were mainly involved in the biological processes such as oxidation-reduction process,proteolysis,mitotic nuclear division and so on.CC is mainly concentrated on extracellular exosome,extracellular region,extracellular space and others.MF is mainly enriched in functions of heme binding,iron ion binding,chromatin binding and all.The pathway is enriched in metabolic pathways,alanine,aspartate and glutamate metabolism and tryptophan metabolism.10 key genes were obtained from 13 hub genes,and the key genes had statistically significant in mutation,co-expression and prognosis(P<0.05).Based on the above key genes,resveratrol,triptolide,andrographolide,Scutellaria baicalensis extract,Silybin,Curcumin,Quercetin,cryptotanshinone and so on,which candidate chemical compound were selected.Conclusion In this study,several key genes and potential drugs were found through data mining and bioinformatics analysis,which provided a reference for the identification of potential therapeutic targets and the optimization of drug regimens for clinical HBV related liver cancer.