HER-2阴性乳腺癌新靶向基因的生物信息学分析  

Using Bioinformatics Analysis for Screening for a New Potential Target Gene in HER-2 Negative Breast Cancer

作　　者：沈慧丽 李广 宋晶 刘翔宇 冉隆科[3,4] Shen Huili;Li Guang;Song Jing;Liu Xiangyu;Ran Longke(Academy of Pediatrics, Chongqing Medical University, Chongqing 400016;Department of hioinformatics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016;Center for molecular and cancer research, Chongqing Medical University, Chongqing, 400016;Department of forensic medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016)

机构地区：[1]重庆医科大学儿科学院,重庆400016 [2]重庆医科大学基础医学院生物信息学教研室,重庆400016 [3]重庆医科大学分子与肿瘤研究中心,重庆400016 [4]重庆医科大学基础医学院法医学教研室,重庆400016

出　　处：《基因组学与应用生物学》2018年第5期2287-2292,共6页Genomics and Applied Biology

基　　金：重庆市渝中区科委项目(20150107)资助

摘　　要：利用生物信息学方法研究HER-2阴性乳腺癌的潜在靶向基因、信号传导通路及分子机制。从公众数据库（gene expression omnibus,GEO）下载HER-2阴性乳腺癌患者和正常女性上皮细胞基因芯片数据,运用RMA算法进行数据预处理,运用R语言LIMMA的包选出差异表达基因。将差异表达基因上传到DAVID在线网站进行富集分析,运用KEGG信号传导通路进行信号传导通路分析,最后用STRING进行蛋白相互作用网络分析（控制差异表达倍数大于2倍,p值小于0.01）,筛出差异表达基因72个（上调基因10个,下调基因62个）。差异基因富集分析结果表明富集程度高的差异基因主要与转录调节、细胞凋亡及细胞外刺激反应等密切相关,信号传导通路分析结果表明差异基因主要与MAPK信号转导通路等密切相关,蛋白共表达网络分析结果表明关键蛋白质为FOS、JUN、KLF6、ATF3、HIST2H2AA4和HIST2H2BE等。HER-2阴性的乳腺癌患者早期差异表达基因表现为下调,HIST2H2AA4和HIST2H2BE可成为其潜在靶向基因,并可作为MAPK信号传导通路中ERK1/2中FOS基因的下游基因,验证需进一步实验。To explor e the potential target genes,signal transduction pathways of HER-2 negative breast cancer using bioinformatics.To clarify the molecular mechanism of HER-2 negative breast cancer.The microarray gene expression profile about the normal epithelial cell for HER-2 negative breast cancer patients and normal female was downloaded from a public database called GEO（Gene Expression Omnibus）.The DEGs（Differential Expression Genes） was identified using the limma package（Linear Models for Microarray data package） after preprocessing the datasets by rma algorithm.Analyses of the GO（Gene Ontology）,signal pathways and protein-protein interaction networks for the DEGs were conducted using the DAVID,STRING and other software.72 DEGs including 10 up-regulated genes and 62 down regulated genes were screened with the ratio being more than 2 times and the p-value being less than 0.01.The enrichment analysis for DEGs showed that the high degree of differences in DEGs was closely related to transcription regulation,cell apoptosis and extracellular stimuli.The signal transduction pathway analysis for DEGs showed that the main signal pathway was mainly related to MAPK signal pathway.The protein-protein interaction analysis for DEGs showed the hug protein was consisted of FOS,JUN,KLF6,ATF3,HIST2 H2 AA4 and HIST2 H2 BE etc.We found the DEGs was down regulated in HER-2 negative breast cancer patients,and HIST2 H2 BE and HIST2 H2 AA4 can be a potential target genes and as a downstream gene after FOS gene at the ERK1/2 pathway in MAPK signal pathway.

关 键 词：乳腺癌 生物信息学 差异表达基因 靶向基因 信号传导通路 

分 类 号：Q811.4[生物学—生物工程] R737.9[医药卫生—肿瘤]