基于生物信息学的酒精性肝病关键基因筛选及验证  

Screening and validation of key genes for alcoholic liver disease based on bioinformatics

作　　者：王一涵 漆光紫[1,5,3] 李文学 岑育芳[2,5,3] 韦俊宏 唐玉航 庞雅琴 WANG Yihan;QI Guangzi;LI Wenxue;CEN Yufang;WEI Junhong;TANG Yuhang;PANG Yaqin(School of Basic Medicine,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;School of Public Health and Management,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;Key Laboratory of Environmental Pollution and Health Risk Assessment,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;School of Laboratory Medicine,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;Key Laboratory of Environment and Population Health Research of Guangxi University Eco-Aluminum Industrial Base,Baise 533000,Guangxi,China;Department of Toxicology and Biochemical Laboratory,Guangzhou Center for Disease Control and Prevention,Guangzhou 510000,Guangdong,China)

机构地区：[1]右江民族医学院基础医学,广西百色533000 [2]江民族医学院公共卫生与管理学院,广西百色533000 [3]右江民族医学院环境污染与健康风险评价重点实验室,广西百色533000 [4]右江民族医学院医学检验学院,广西百色533000 [5]广西高校生态铝工业基地环境与人群健康研究重点实验室,广西百色533000 [6]广东省广州市疾病预防控制中心毒理与生化检验科,广东广州510000

出　　处：《右江医学》2023年第5期389-396,共8页Chinese Youjiang Medical Journal

基　　金：国家自然科学基金(81960595,81360438,81660549);广西自然科学基金(2019JJD140011);2022年右江民族医学院硕士研究生创新计划项目(YXCXJH2022010)。

摘　　要：目的利用生物信息学方法探索酒精性肝病(alcoholic liver disease,ALD)潜在的关键基因并通过实验验证,为寻找ALD潜在的生物标志物提供依据。方法从美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)的公共基因芯片数据平台(Gene Expression Omnibus,GEO)的数据库下载两个基因表达谱芯片(GSE28619和GSE100901),利用GEO2R筛选出酒精性肝病实验组与正常对照组的差异表达基因(differentially expressed genes,DEGs),对DEGs进行基因本体论(gene ontology,GO)与京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路的富集分析,进一步应用STRING数据库构建蛋白质的相互作用网络,用Cytoscape来筛选出关键基因。构建ALD小鼠模型,通过RT-qPCR验证筛选出关键基因。结果总共鉴定出173个DEGs,GO显示DEGs生物学功能主要涉及5个KEGG通路,包括补体和凝血级联、胆固醇代谢、视黄醇代谢、药物代谢-细胞色素P450、胆汁分泌相关信号通路,结合蛋白质相互作用网络(protein-protein interaction,PPI)和CytoHubba的结果,筛选出SERPINC1、AHSG、FGG、FGA、ITIH3、FGB、APOB、ALB和APOH 9个关键基因,通过RT-qPCR检测验证,发现与WT小鼠相比,ALD小鼠肝脏ALB、APOB和FGB的mRNA表达上调(P<0.05),而ITIH3、FGG和SERPINC1的mRNA表达下调(P<0.05)。结论ALB、APOB、FGB、ITIH3、FGG、SERPINC1有望成为ALD潜在的生物标志物。Objective To explore the potential key genes of alcoholic liver disease(ALD)by bioinformatics methods and to validate them through experiments,so as to provide basis for searching for potential biomarkers of ALD.Methods Two gene expression profile chips(GSE28619 and GSE100901)were downloaded from the database of the public GeneChip Data Platform(Gene Expression Omnibus,GEO)of the National Center for Biotechnology Information(NCBI)in the United States.GEO2R was used to select differentially expressed genes(DEGs)in ALD group and control group.The enrichment analysis of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)signaling pathways in DEGs was conducted.Furthermore,STRING database was applied to construct the interaction network of proteins,and key genes were screened by Cytoscape.ALD mice models were constructed and key genes were screened by RT-qPCR validation.Results A total of 173 DEGs were identified.GO showed that the biological functions of DEGs mainly involved in five KEGG pathways,including complement and coagulation cascade,cholesterol metabolism,retinol metabolism,drug metabolism-cytochrome P450,and bile secretion-related signaling pathways.Based on the results of protein-protein interaction network(PPI)and CytoHubba,9 key genes,namely,SERPINC1,AHSG,FGG,FGA,ITIH3,FGB,APOB,ALB,and APOH,were screened out.RT-qPCR detection found that compared with WT mice,the mRNA expressions of ALB,APOB,and FGB in the liver of ALD mice upregulated(P<0.05),while the mRNA expressions of ITIH3,FGG,and SERPINC1 downregulated(P<0.05).Conclusion ALB,APOB,FGB,ITIH3,FGG and SERPINC1 are expected to be potential biomarkers for ALD.

关 键 词：生物信息学 酒精性肝病 基因 生物标志物 

分 类 号：R575.5[医药卫生—消化系统] Q811.4[医药卫生—内科学]