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EZH2在乳腺癌中的差异表达及临床意义
引用本文:赵昕辉,杨万里,张浩萌,武 赫,韩晓刚,孟庆杰,吕勇刚.EZH2在乳腺癌中的差异表达及临床意义[J].现代肿瘤医学,2020,0(23):4101-4107.
作者姓名:赵昕辉  杨万里  张浩萌  武 赫  韩晓刚  孟庆杰  吕勇刚
作者单位:1.西北大学附属医院,西安市第三医院甲乳外科,陕西 西安 710018;2.空军军医大学西京消化病医院,肿瘤生物学国家重点实验室,陕西 西安 710032
基金项目:西安市科学技术局科技计划项目(编号:2019115213YX007SF040);西安市卫生和计划生育委员会2019年卫生科研人才项目(编号:J201902045)
摘    要:目的:利用整合生物信息学手段分析EZH2(enhancer of zeste 2 polycomb repressive complex 2 subunit)基因在乳腺癌中的表达及其临床意义。方法:在肿瘤基因组计划数据库(The Cancer Genome Atlas,TCGA)中下载乳腺癌与正常乳腺组织的基因表达谱数据,进一步利用Ualcan数据库和人类蛋白质图谱(The Human Protein Atlas)数据库数据分析EZH2基因在乳腺癌中的mRNA及蛋白表达水平。利用Ualcan数据库分析EZH2基因的甲基化水平并筛选其共表达基因;对EZH2及其共表达基因进行GO(Gene Ontology)富集分析和KEGG通路分析以明确EZH2的共表达基因参与的生物学过程和相关通路;使用Kaplan-Meier生存分析法分析乳腺癌患者的总生存期、无病生存期、无远处转移生存期及后进展生存期与EZH2基因表达水平的关系并绘制生存曲线。结果:与正常乳腺组织相比,EZH2在乳腺癌组织中的mRNA及蛋白表达量明显升高。而EZH2的甲基化程度在乳腺癌组织与正常乳腺组织中则差异不明显。同时,EZH2的表达水平与年龄、乳腺癌分期及乳腺癌分子分型等因素密切相关。EZH2及其共表达基因主要参与了核碱基的调节、细胞周期调控、染色体分离、DNA复制、DNA修复等生物学过程,并参与了细胞周期、DNA 复制、M/G1期转化、M期、有丝分裂前中期、ATM通路等生物学通路。此外,EZH2基因表达水平高的乳腺癌患者的总生存期、无病生存期、无远处转移生存期及后进展生存期均明显低于EZH2基因低表达的患者。结论:EZH2在乳腺癌组织中高表达并且与患者不良预后密切相关。同时,EZH2的表达水平与乳腺癌的发生、发展密切相关。EZH2在乳腺癌诊断、靶向治疗及预后分析中具有重要的临床意义。

关 键 词:乳腺癌  EZH2  TCGA  生物标志物  生物信息学分析

Integrated bioinformatics analysis for expression and function of EZH2 in breast cancer
ZHAO Xinhui,YANG Wanli,ZHANG Haomeng,WU He,HAN Xiaogang,MENG Qingjie,LYU Yonggang.Integrated bioinformatics analysis for expression and function of EZH2 in breast cancer[J].Journal of Modern Oncology,2020,0(23):4101-4107.
Authors:ZHAO Xinhui  YANG Wanli  ZHANG Haomeng  WU He  HAN Xiaogang  MENG Qingjie  LYU Yonggang
Affiliation:1.Department of Thyroid and Breast Surgery,the Affiliated Hospital of Northwest University & Xi'an No.3 Hospital,Shaanxi Xi'an 710018,China;2.State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Air Force Medical University,Shaanxi Xi'an 710032,China.
Abstract:Objective:To analyze the expression and roles of enhancer of zeste 2 polycomb repressive complex 2 subunit(EZH2)in breast cancer(BC)via integrated bioinformatics analysis.Methods:The expression data of EZH2 in normal breast tissues and BC tissues were downloaded from The Cancer Genome Atlas(TCGA)database.The mRNA and protein levels of EZH2 in BC tissues were analyzed using Ualcan online tool and The Human Protein Atlas database,respectively.Gene Ontology(GO)and KEGG analyses were conducted for the co-expressed genes of EZH2.Kaplan-Meier plotter database was used to analyze the prognostic value of EZH2 in BC patients.Results:The mRNA and protein levels of EZH2 were significantly overexpressed in BC tissues compared to normal breast tissues.However,the DNA methylation status of EZH2 showed no significantly difference between BC patients and normal controls.Besides,the level of EZH2 in BC tissues was significantly different in patients from different subgroups.The GO and KEGG analyses showed that EZH2 and its co-expressed genes in BC were closely associated with regulation of nucleobase,regulation of cell cycle,chromosome segregation,DNA replication,ATM pathways,and other related pathways.Importantly,high expression of EZH2 predicted poor survival rates in BC patients.Conclusion:Our results showed that the EZH2 was highly expressed in BC and predicted poor survival of BC patients.Moreover,EZH2 might play a significant role in the development and progression of BC,thus it could be utilized as a biomarker and therapeutic target for diagnosis,prognosis,and treatment of BC.
Keywords:breast cancer  EZH2  TCGA  biomarker  bioinformatics
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