基于生物学数据库GATA3在乳腺癌中表达和预后及相关分子信号分析  

Bioinformatics analysis of GATA3 expression,prognosis and related molecular signals in breast cancer based on biological database

作　　者：张然 王健 ZHANG Ran;WANG Jian(Department of Oncology Surgery,Tianjin Medical University Cancer Institute and Hospital,Tianjin Cancer Hospital Airport Free Trade Zone Hospital,National Clinical Research Center of Cancer,Key Laboratory of Breast Cancer Prevention and Therapy,Key Laboratory of Cancer Prevention and Therapy,Tianjin Clinical Research Center for Cancer,Tianjin 300060,China)

机构地区：[1]天津医科大学肿瘤医院天津市肿瘤医院空港医院综合外科·国家肿瘤临床医学研究中心·乳腺癌防治教育部重点实验室·天津市肿瘤防治重点实验室·天津市恶性肿瘤临床医学研究中心,天津300060

出　　处：《中华肿瘤防治杂志》2021年第8期592-597,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81700183,81602020);天津医科大学科学基金(2016KYZQ05)。

摘　　要：目的基于全基因组表达谱数据库,探讨新兴肿瘤治疗靶点GATA家族的GATA3在乳腺癌中的mRNA表达水平,及与乳腺癌患者预后的关系和分子机制。方法通过UALCAN在线分析乳腺癌组织和正常组织中差异表达的基因。采用Kaplan-Meier Plotter进行GATA3表达水平与乳腺癌患者的生存分析。应用DAVID(The Database for Annotation,Visualization and Integrated Discovery)网站将筛选出的差异基因进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)信号转导通路富集分析。通过STRING在线软件和Cytoscape软件进行GATA3相关的蛋白互作网络(PPI)分析。结果相比正常乳腺组织(中位值=97.42,四分位间距=50.07),GATA3在乳腺癌组织高表达(中位值=294.39,四分位间距=108.71),差异有统计学意义,P<0.001。生存分析中,GATA3高表达的总体乳腺癌患者无复发生存期(RFS)比低表达患者延长(HR=0.71,95%CI:0.70~0.84,P<0.05),GATA3高表达的ER阳性(HR=0.82,95%CI:0.67~0.99,P<0.05)或淋巴结阳性(HR=0.62,95%CI:0.49~0.77,P<0.01)的乳腺癌患者预后较好,差异有统计学意义。GO富集分析提示,GATA3涉及细胞增殖、细胞迁徙、对雌激素的反应及对药物的反应等多个细胞生物学过程。蛋白互作网络证实,GATA3与ESR1、FOXA1等是ER信号通路中的重要分子信号。结论GATA3在乳腺癌组织中高表达,与乳腺癌好的预后有关联,GATA3参与对雌激素的反应等通路,同时与ER信号通路的多个基因存在相互作用,是潜在的治疗靶点。Objective To evaluate the expression and prognostic values of endothelial transcription factor 3(GATA3)in breast cancer and explore GATA3-induced molecular mechanism and signaling pathways in the pathogenesis of breast cancer.Methods Gene expression profiles(GSE15852)were downloaded from the Gene Expression Omnibus(GEO)database.The difference of mRNA expression level of GATA3 between breast cancer tissues and normal tissues were evaluated in the UALCAN database.The prognostic values of GATA3 assessed by displaying the relapse-free survival(RFS)in breast cancer according to clinicopathological factors were analyzed by Kaplan-Meier plotter.Differential expression genes(DEGs)were screened using the GEO2 R tool,with the criteria of P<0.05.Enriched gene Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways of differential expression genes(DEGs)were conducted by The Database for Annotation,Visualization and Integrated Discovery(DAVID)with P<0.05 as thresholds.STRING and Cytoscape were performed to establish the GATA3-related protein-protein interaction network(PPI).Results The expression of GATA3 was significantly higher in breast cancer samples(M=294.39,IQR=108.71)compared with normal samples(M=97.42,IQR=50.07,P<0.01).In subgroup analysis,up-regulated expression of GATA3 was significantly correlated to better RFS in ER positive(HR=0.82,95%CI:0.67-0.99,P<0.05)and node positive(HR=0.62,95%CI:0.49-0.77,P<0.01)breast cancer patients.Significantly involved in enriched GO terms for biological process,GATA3 were negative regulation of cell proliferation,positive regulation of endothelial cell migration,response to estrogen and response to drug.PPI network showed that GATA3 was related with ESR1,FOXA1 in ERαsignaling pathway.Conclusions The expression level of GATA3 is higher in breast cancer compared with other tumor tissues.High expression level of GATA3 is associated with favorable relapse-free survival,especially in patients with ER positive breast cancer.GATA3 participates in response to estro

关 键 词：GATA3 乳腺癌 生存分析 生物信息学 

分 类 号：R737.9[医药卫生—肿瘤]