磷脂酰肌醇蛋白聚糖3和泛素D基因在肝细胞癌中的异常表达及其相互作用  

Abnormal expression of glypican-3 and ubiquitin D in hepatocellular carcinoma and the associated interaction

作　　者：谭玉靓 戴姿薇 唐标 TAN Yu-jing;DAI Zi-wei;TANG Biao(Grade 2016,Medical School,Hu’nan University of Chinese Medicine,Changsha 410208,China;Department of Physiology,Medical School,Hu’nan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学医学院,长沙410208 [2]湖南中医药大学医学院生理学教研室,长沙410208

出　　处：《解剖学报》2021年第5期744-750,共7页Acta Anatomica Sinica

基　　金：2019年湖南省教育厅科学研究优秀青年项目(19B436)。

摘　　要：目的利用基因组学和表观遗传组学分析工具,分析磷脂酰肌醇蛋白聚糖3(GPC3)和泛素D(UBD)在肝细胞癌(HCC)中的异常表达情况,以及两者对HCC患者预后的影响。方法利用ULCAN(http://ualan.path.uab.edu)和Gene Expression Profiling Interative Analysis(GEPIA)数据库,分析UBD和GPC3在正常肝组织和HCC组织的异常表达情况和甲基化水平,以及对HCC患者生存的影响。利用Gene Cards数据库分析UBD和GPC3的定位。利用STRING数据库对UBD和GPC3分别构建蛋白质互相作用(PPI)网络,并对UBD和GPC3进行基因注释。基于皮尔森相关系数,计算UBD和GPC3在HCC发生发展中的关联。结果UBD和GPC3在HCC组织中表达上调,启动子甲基化水平下降。UBD位于6p22.1,主要表达于细胞核;GPC3位于Xq26.2,主要表达于细胞膜、细胞外基质、内质网、溶酶体和高尔基体。富集分析显示,UBD主要与蛋白酶体活动相关:翻译后蛋白修饰、泛素化和去泛素化;GPC3主要参与黏多糖的生物合成和分解过程,介导的生物通路主要涉及癌症多聚糖、细胞外基质受体相互作用和细胞黏附分子。关联分析显示,UBD和GPC3成线性正相关,共同调控HCC的发生发展。预后分析显示,GPC3对HCC的预后有明显的影响。结论UBD和GPC3在HCC的表达均上调,甲基化水平均降低,GPC3对HCC的预后影响较大,或许可以作为预后评估的生物标志。Objective To explore the abnormal expression of ubiquitin D(UBD)and glypican-3(GPC3)among patients of hepatocellular carcinoma(HCC)by using analysis tools of genomics and epigenetics,so as to study their prognostic effects.Methods The online tools called ULCAN(http://ualan.path.uab.edu)and Gene Expression Profiling Interative Analysis(GEPIA)were used to perform expression analysis in genomics and epigenetics of UBD and GPC3.Moreover,GEPIA was conducted to evaluate the survival effects on HCC patients.The Gene Cards was used to find the localization of UBD and GPC3 in tumor tissue and normal tissue.The STRING was utilized to perform the construction of PPI network and gene annotation.The correlation between UBD and GPC3 in progress of HCC was revealed based on Pearson correlation coefficient.Results UBD and GPC3 were dramatically up-regulated in HCC tissues,with downregulation of methylation level.UBD was located in 6 p22.1 with primary expression in the nucleus,while GPC3 was located in Xq26.2 with main expression in the plasma membrane,extracellular matrix,endoplasmic reticulum,lysosome and golgi apparatus.The enrichment analysis showed that,UBD was enriched in activities involving proteasome,such as post-translation protein modification,ubiquitination and deubiquitination.GPC3 was enriched in the biosynthetic and catabolic process of glycosaminoglycan,possessed relationship with proteoglycans in cancer,ECM-receptor interaction,cell adhesion molecules(CAMs).Both of UBD and GPC3 were shown to exhibit a positive linear correlation,which suggested that GPC3 and UBD mediated the pathological process of HCC in cooperation.The survival analysis showed that,GPC3 exhibited a critical effect on survival of HCC patients.Conclusion UBD and GPC3 represent up-regulation in tumor tissue,in which GPC3 possesses a greater impact on the prognosis of HCC.GPC3 could be potential to serve as a practical biomarker for early diagnosis and medical intervention.

关 键 词：肝细胞癌 生物信息学 泛素D 磷脂酰肌醇蛋白聚糖3 GEPIA数据库 人 

分 类 号：R378.3[医药卫生—病原生物学]