基于数据挖掘分析ONECUT2基因在胃癌的表达及与幽门螺杆菌感染的相关性  

Expression of ONECUT2 in gastric cancer and its relationship with Helicobacter pylori infection: a data-mining analysis based on public database

作　　者：米阳 刘斌 任飞飞 黄煌[1,2] 梅璐[1,2] 于泳[1,2] 汤有才[1,4] 郑鹏远[1,2] MI Yang;LIU Bin;REN Feifei;HUANG Huang;MEI Lu;YU Yong;TANG Youcai;ZHENG Pengyuan(Marshall Medical Research Center,the Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第五附属医院马歇尔医学研究中心,河南郑州450052 [2]郑州大学第五附属医院消化内科,河南郑州450052 [3]郑州大学医学科学院,河南郑州450052 [4]郑州大学第五附属医院儿科,河南郑州450052

出　　处：《中国微生态学杂志》2020年第5期527-532,共6页Chinese Journal of Microecology

基　　金：河南省科技攻关国际科技合作项目(182102410018);国家自然科学基金(81370494);河南省医学科技攻关项目(2018020224);河南省医疗服务能力提升工程(豫卫医[2017]66号);河南省科技厅国际合作项目(172102410014);郑州协同创新重大专项(18XTZX12003)。

摘　　要：目的分析ONECUT2基因在胃癌中的表达及其与幽门螺杆菌(Helicobacter pylori,H.pylori)感染的相关性。方法(1)利用Oncomine数据库、TCGA数据库分析ONECUT2基因在胃癌中的表达,R软件包进行基因的共聚类微阵列数据分析。(2)利用Kaplan-Meier Plotter数据库和GEPIA数据库分析ONECUT2差异表达与胃癌患者预后的关系。(3)利用生物信息学功能注释数据平台DAVID对胃癌中与ONECUT2基因表达正相关的前200个基因进行功能富集分析。(4)利用GEO数据库中的数据分析H.pylori感染与ONECUT2表达的相关性。结果(1)Oncomine数据库中的数据在胃癌、膀胱癌等8种肿瘤中共有14项研究显示ONECUT2基因在肿瘤组织中的高表达;其中胃癌相关的有两项(t=6.064,P<0.0001;t=4.335,P<0.0001);TCGA数据库的数据也证实胃癌中ONECUT2高表达(t=6.680,P<0.001)。(2)胃癌中ONECUT2与EHF、FUT6、TNFRSF11A、RSAEF、EPCAM等20个基因有较高的共表达。(3)GO分析发现胃癌中ONECUT2富集在分子结构活性等相关的基因功能上;而KEGG富集分析发现ONECUT2富集于紧密连接功能等6个通路。(4)Kaplan-Meier Plotter数据库中207676-at芯片结果显示ONECUT2高表达组患者远期生存率下降(P<0.001);GEPIA数据库中的分析结果同样显示ONECUT2高表达组患者其总体生存率(P<0.05)和无病生存率(P<0.01)下降。GEO数据库中GSE74577(P=0.005)、GSE70394(P=0.034)和GSE25146(P=0.036)三个数据集均显示H.pylori感染AGS和GES-1细胞系后ONECUT2表达上调。结论ONECUT2在胃癌中高表达,且与胃癌一类致癌原H.pylori感染相关。ONECUT2高表达组患者远期生存率下降,表明其与胃癌发生发展密切相关,可能成为胃癌治疗的新靶点。Objective To analyze the gene expression of ONECUT2 in gastric cancer(GC)and its relationship with Helicobacter pylori(H.pylori)infection.Methods(1)Oncomine,TCGA database were used for analyzing the expression of ONECUT2 in GC,and Microarray Data Analysis Based on Clustering Algorithms were carry out by using R software package.(2)Kaplan-Meier Plotter and GEPIA database were used for evaluating the correlation between the differential expression of ONECUT2 and prognosis of GC.(3)GO and KEGG pathway analysis were performed at DAVID platform.(4)The correlation between H.pylori infection and ONECUT2 expression was analyzed using data from GEO database.Results(1)Oncomine database showed that ONECUT2 was over-express in 14 studies including 8 kinds of tumor tissues such as GC,bladder cancer,where 2 studies were about GC(t=6.064,P<0.0001;t=4.335,P<0.0001);Consistently,TCGA database also confirmed the high expression of ONECUT2 in GC(t=6.680,P<0.001).(2)ONECUT2 was co-expressed with 20 genes,such as EHF,FUT6,TNFRSF11 A,RSAEF and EPCAM,etc.(3)GO function and KEGG pathway analysis showed that ONECUT2 concentrated on the molecule activity and six pathways about tight junction.(4)Microarray data(ID:207676-at)from K-M plotter database showed long-term survival rate of GC patients decreased correlated with high expression of ONECUT2(P<0.001);Similarly,GEPIA database analysis also showed that GC patients with high expression of ONECUT2 correlated with decreased overall survival(P<0.05)and disease-free survival(P<0.01).GSE74577(P=0.005),GSE70394(P=0.034)and GSE25146(P=0.036)from GEO database shown high expression of ONECUT2 upon Hp infection in AGS and GES-1 cell lines.Conclusion High expression of ONECUT2 associated with H.pylori infection and decreased long-term survival rate of GC patients,which shown its positive correlation with GC development and potential of new target for GC therapy.

关 键 词：ONECUT2 胃癌 Oncomine K-M plotter GEO数据库 幽门螺杆菌感染 

分 类 号：R573[医药卫生—消化系统]