miR-652在HBV相关肝细胞癌中的表达、临床意义及靶基因功能分析  

Expression,Clinical Significance and Target Gene Function of MiR-652 in HBV-Related Hepatocellular Carcinoma

作　　者：王雪容[1] 唐娟[1] Wang Xuerong;Tang Juan(The First People's Hospital of Zigong,Zigong,Sichuan 643000,China)

机构地区：[1]自贡市第一人民医院感染科,四川自贡643000

出　　处：《四川医学》2020年第12期1237-1244,共8页Sichuan Medical Journal

摘　　要：目的探讨miR-652在HBV相关肝细胞癌(HCC)中的表达情况及临床意义,分析靶基因功能并完成核心基因发掘。方法查找GEO数据库HBV相关HCC芯片,采用GEO2R分析得到前十位差异表达miRNAs。HCC肿瘤组织中miR-652表达检测采用miRNA荧光定量检测技术。比较分析不同临床特征分组情况下miR-652表达差异。MiR-652与肝癌患者生存率分析使用Kaplan-Meier plotter数据库。MiR-652靶基因分析使用miRWalk 2.0在线软件。靶基因GO功能注释和KEGG通路富集使用在线软件Web Gestalt。蛋白互作网络(PPI)分析采用在线软件string,并联合Cytoscape软件完成靶蛋白PPI构建及核心基因发掘。结果芯片数据发掘表明miR-652在HBV相关肝癌中表达显著升高。收集的肿瘤标本检测分析显示HBV感染HCC患者中miR-652表达显著高于未感染HBV的HCC患者。按照临床特征分组分析显示,miR-652表达在病理分级Ⅲ~Ⅳ级组显著高于Ⅰ~Ⅱ级组,在转移组显著高于未转移组,而在HBV DNA载量、肿瘤直径、TNM分期分组中无显著性差异。按照肿瘤直径、TNM分期、病理分级、肿瘤转移4个临床指标对HBV相关HCC和无HBV相关HCC作分组对比发现miR-652表达只在HBV相关HCC组的病理分级和肿瘤转移分层中对比表现出显著性差异。生存分析结果表明肝癌组织中miR-625高表达类型的肝癌患者10年期总生存率显著低于肝癌组织中miR-625低表达类型的肝癌患者。取交集后共获得miR-652调控的靶基因34个。GO富集分析显示miR-625的靶基因参与的功能作用主要指向RNA的转录翻译过程。对靶基因的KEGG分析显示主要富集在粘多糖生物合成与降解、β-丙氨酸代谢、RNA降解、半胱氨酸和蛋氨酸代谢、精氨酸和脯氨酸代谢、嘌呤代谢等信号通路。蛋白网络互作和核心基因挖掘显示PTEN为靶基因集的核心蛋白。结论 miR-652与HBV患者的肝癌发生发展密切相关,并可能通过靶向PTEN为核心基因�Objective To investigate expression and clinical significance of miR-652 in HBV-related hepatocellular carcinoma(HCC),analyze target genes function,and complete core genes discovery.Methods HBV-related HCC chips in GEO database were searched and GEO2R was used to obtain top ten differentially expressed miRNAs.The miR-652 expression in HCC tumor tissues was detected by miRNA fluorescence quantitative detection technology.Differences in miR-652 expression under different clinical characteristics were compared and analyzed.Kaplan-Meier plotter database was used to analyze MiR-652 and survival rate of liver cancer patients.MiR-652 target gene was analyzed by miRWalk 2.0 online software.Online software Web Gestalt was used for target gene GO function annotation and KEGG pathway enrichment.Online software string was used for protein-protein interaction network(PPI)analysis.PPI combined with Cytoscape software were used to complete construction of target protein PPI and discovery of core genes.Results Microarray data showed that miR-652 expression was significantly increased in HBV-related liver cancer.Detection and analysis of collected tumor specimens showed that miR-652 expression in HCC patients with HBV infection was significantly higher than that in HCC patients without HBV infection.According to clinical characteristics by grouping analysis showed that miR-652 expression in pathological gradeⅢ~Ⅳgroup was significantly higher than inⅠ~Ⅱgroup.And it was significantly higher in metastatic group than in non-metastatic group.There were no significant differences in HBV DNA load,tumor diameter,and TNM staging groups.HBV-related HCC and non-HBV-related HCC were grouped and compared by four clinical indexes:tumor diameter,TNM stage,pathological grade and tumor metastasis.It was found that miR-652 expression only showed significant difference in pathological grade and tumor metastasis stratification in HBV-related HCC group.Survival analysis results showed that 10-year overall survival rate of liver cancer patient

关 键 词：miR-652 肝细胞癌 HBV 生物信息学 PTEN 

分 类 号：R735.7[医药卫生—肿瘤]