拓扑异构酶Ⅱα(TOP2A)基因的表达与CD4^(+)T细胞在肝细胞癌中的数量相关性及临床预后意义  

Correlation between TOP2A gene expression and the number of CD4^(+)T cells in hepatocellular carcinoma and its clinical prognostic significance

作　　者：卢兴浩[1,2] 俞鹏 陶恒[1,2] 陈云帆 陆进[1,2] LU Xinghao;YU Peng;TAO Heng;CHEN Yunfan;LU Jin(Department of Human Anatomy,Bengbu Medical College,Bengbu 233030,China;Digital Medicine and Smart Health Anhui Key Laboratory,Bengbu Medical College,Bengbu 233030,China)

机构地区：[1]蚌埠医学院人体解剖学教研室,安徽蚌埠233030 [2]蚌埠医学院数字医学与智慧健康安徽省重点实验室,安徽蚌埠233030

出　　处：《细胞与分子免疫学杂志》2022年第1期24-31,共8页Chinese Journal of Cellular and Molecular Immunology

基　　金：安徽省教育厅自然科学研究重点项目(KJ2019A0338);教育部产学合作协同育人项目(202101160001)。

摘　　要：目的分析拓扑异构酶Ⅱα(TOP2A)基因的表达与CD4^(+)T细胞在肝细胞癌(HCC)中的数量相关性及临床预后意义。方法利用基因注释资源数据库(BioGPS)、基因表达谱交互作用分析(GEPIA)和Kaplan-Meier Plotter数据库分析TOP2A mRNA在正常肝组织和HCC组织中的表达以及对HCC患者生存预后意义;利用GENE和Metascape数据库分析TOP2A的共表达基因及其基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析;利用Sangerbox数据库分析TOP2A基因与微卫星不稳定(MSI)和DNA错配修复基因的相关性;再分别利用TISIDB和TIMER数据库分析TOP2A基因与CD4^(+)T细胞和各种免疫细胞的关系,并分析CD4^(+)T细胞对HCC患者生存预后的影响。结果TOP2A mRNA在正常肝组织和CD4^(+)T细胞中表达不显著,而在HCC组织中显著高表达,不利于患者的生存预后;TOP2A共表达基因的GO功能主要富集在细胞有丝分裂和细胞增殖上,而KEGG主要富集在细胞循环和铂类化疗药物耐药通路;TOP2A基因的表达与MSI、DNA错配修复基因MutS同源物2(MSH2)与MSH6、肿瘤细胞纯度以及各种免疫细胞的数量显著正相关;各种免疫细胞在HCC中均发生一定的拷贝数变异,但仅有CD4^(+)T细胞的数量对HCC患者生存预后有显著影响。结论HCC组织中TOP2A mRNA表达与CD4^(+)T细胞数量呈正相关,不利于HCC患者的生存预后。Objective To analyze the correlation between the expression of TOP2A gene and the proportion of CD4^(+)T cells in hepatocellular carcinoma(HCC)and its clinical prognostic significance.Methods The expression of TOP2A mRNA in normal liver tissues and HCC tissues and its significance for survival and prognosis of HCC patients were analyzed by BioGPS,GEPIA and Kaplan-Meier Plotter databases.The coexpression gene of TOP2A and its GO function were analyzed using GENE and Metascape databases,along with the KEGG pathway enrichment analysis.The correlation between TOP2A and microsatellite instability(MSI)and DNA repair gene was analyzed by Sangerbox database.Then,the correlation between TOP2A gene and CD4^(+)T cells and various immune cells was analyzed by TISIDB and TIMER database,and analysis was also performed regarding the effect of CD4^(+)T cells on the survival and prognosis of HCC patients.Results TOP2A mRNA is not significantly expressed in normal liver tissues and CD4^(+)T cells,but is significantly expressed in HCC tissue,which is not conducive to the survival and prognosis of patients.The GO function of TOP2A coexpression gene is mainly enriched in cell mitosis and cell proliferation,while KEGG is mainly enriched in cell cycle and platinum drug resistance pathway.The expression of TOP2A is positively correlated with MSI,MSH2 and MSH6 of DNA repair gene,the purity of tumor cells and the numbers of various immune cells.All kinds of immune cells reported certain copy number variation in HCC,but only the numbers of CD4^(+)T cells showed a significant effect on the survival and prognosis of HCC patients.Conclusion There is a significant positive correlation between the expression of TOP2A mRNA and the number of CD4^(+)T cells in HCC,which is not conducive to the survival and prognosis of HCC patients.

关 键 词：拓扑异构酶Ⅱα(TOP2A) 总体生存 肿瘤 肝癌 

分 类 号：S853.53[农业科学—临床兽医学] R735.7[农业科学—兽医学]