酒精性肝炎自噬关键基因的筛选及生物信息学分析  

Screening and bioinformatics analysis of key autophagy-related genes in alcoholic hepatitis

作　　者：袁超[1] 练庆海 尼贝贝 许燕 张彤[1] 张剑[1] Yuan Chao;Lian Qinghai;Ni Beibei;Xu Yan;Zhang Tong;Zhang Jian(不详;Department of Hepatic Surgery,Liver Transplantation Center,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院肝脏外科暨肝移植中心,广州510630 [2]中山大学附属第三医院疫苗研究所,广州510630 [3]中山大学附属第三医院生物治疗中心,广州510630

出　　处：《器官移植》2024年第1期90-101,共12页Organ Transplantation

基　　金：广东省自然科学基金面上项目(2019A1515011850、2022A1515012224)。

摘　　要：目的筛选酒精性肝炎(AH)的自噬关键基因,探讨AH潜在的生物标志物和治疗靶点。方法采用基因表达综合数据库(GEO)中的2个AH基因芯片和从MSigDB、GeneCards数据库中获得的自噬相关数据集,通过加权基因共表达网络分析(WGCNA)获取关键基因。对筛选的关键基因进行基因本体(GO)、京都基因和基因组百科全书(KEGG)功能富集分析,蛋白质相互作用(PPI)分析,免疫浸润分析,构建信使RNA(mRNA)-微小RNA(miRNA)网络,进行酒精性肝病不同分期的自噬相关关键基因的表达差异分析,并进一步通过实时荧光定量逆转录聚合酶链反应(RT-qPCR)在AH患者和小鼠肝脏组织中验证。结果本研究筛选得到了11个与AH自噬相关的基因(EEF1A2、CFTR、SOX4、TREM2、CTHRC1、HSPB8、TUBB3、PRKAA2、RNASE1、MTCL1、HGF),均为上调基因。在AH患者和小鼠肝脏组织中,SOX4、TREM2、HSPB8、PRKAA2在AH组中的相对表达量均高于对照组。结论SOX4、TREM2、HSPB8、PRKAA2可能是AH潜在的生物标志物和治疗靶点。Objective To screen key autophagy-related genes in alcoholic hepatitis(AH)and investigate potential biomarkers and therapeutic targets for AH.Methods Two AH gene chips in Gene Expression Omnibus(GEO)and autophagy-related data sets obtained from MSigDB and GeneCards databases were used,and the key genes were verified and obtained by weighted gene co-expression network analysis(WGCNA).The screened key genes were subject to gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein-protein interaction(PPI)and immune infiltration analyses.Messenger RNA(mRNA)-microRNA(miRNA)network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH,which were further validated by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)in the liver tissues of AH patients and mice.Results Eleven autophagy-related genes were screened in AH(EEF1A2,CFTR,SOX4,TREM2,CTHRC1,HSPB8,TUBB3,PRKAA2,RNASE1,MTCL1 and HGF),all of which were up-regulated.In the liver tissues of AH patients and mice,the relative expression levels of SOX4,TREM2,HSPB8 and PRKAA2 in the AH group were higher than those in the control group.Conclusions SOX4,TREM2,HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

关 键 词：酒精性肝炎 自噬 关键基因 生物信息学 加权基因共表达网络分析(WGCNA) 基因本体(GO) 京都基因和基因组百科全书(KEGG) 蛋白质相互作用(PPI) 

分 类 号：R617[医药卫生—外科学] R318.04[医药卫生—临床医学]