人胃肠道和胃肠外间质瘤microRNA表达谱的比较  

Comparative analysis of microRNA expression profiles between human gastrointestinal stromal tumors and extra-gastrointestinal stromal tumors

作　　者：林慧[1] 张秀敏[1] 李增山[1] 

机构地区：[1]第四军医大学基础部病理与病理生理学教研室,陕西西安710032

出　　处：《中国肿瘤生物治疗杂志》2011年第2期190-195,共6页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No.30901735);西安市科技计划项目[No.SF1028(4)]~~

摘　　要：目的:比较消化道原发胃肠道间质瘤(gastrointestinal stromal tumors,GISTs)与胃肠外间质瘤(extra-gastrointestinal stromaltumors,EGISTs)microRNA(miRNA)表达谱的差异,分析其与肿瘤原发部位、突变类型等因素间的关系。方法:收集西京医院病理科的8例石蜡样本(5例GISTs、3例EGISTs),利用安捷伦人miRNA表达谱芯片(芯片覆盖866个人miRNA)进行分析。同时通过PCR扩增后直接测序,明确8例样本的基因突变类型。结果:芯片数据经非监督层次聚类分析,显示8例样本分为3簇,具有相同突变类型的1例胃部GIST和1例EGIST构成第1簇,2例胃部GISTs构成第2簇,其余4例(2例小肠GISTs和2例EGISTs)构成第3簇。将5例GISTs按部位分成2组(胃部和肠道),3例EGISTs分别加入miRNA表型相似的组,2组比较后发现12个miRNA表达有显著差异;预测的靶基因多数参与KIT/PDGFRA的信号转导,其中有5个在肠道组显著下调,部分已有报道与肿瘤的演进相关。比较GISTs和EGISTs的表达谱,发现仅有3个miRNA的表达差异具有统计学意义。结论:GISTs和EGISTs的miRNA表型相似,均与肿瘤部位及突变类型关系密切,因此miRNA表型的分析可能有助于GISTs在分子水平上的分类。Objective：To compare the microRNA expression profiles between gastrointestinal stromal tumors（GISTs） and extra-gastrointestinal stromal tumors（EGISTs）,and to evaluate their relationship with primary sites and mutant status of tumors.Methods： Formalin-fixed paraffin-embedded tissues of 5 GISTs and 3 EGISTs were evaluated for differential microRNA（miRNA） expression signatures using Agilent microarrays containing 866 human miRNAs and mutation status of these samples were analyzed by PCR amplification and direct sequencing.Results： Unsupervised hierarchical clustering analysis revealed that 8 samples had been divided into 3 clusters.One gastric GIST and 1 EGIST with the same mutation grouped together and the remaining 2 gastric GISTs also formed a cluster.The other 4 samples including 2 intestinal GISTs and 2 EGISTs could be divided into a third separate cluster.And then we divided 5 GSITs samples into 2 groups according to their anatomical location（stomach and intestine） and assigned 3 EGISTs samples to the group with a similar miRNA expression pattern.Twelve miRNAs,most of which were predicted to participate in the regulation of KIT/PDGFRA signaling,were found to be differentially expressed between the two groups;among them,5 miRNAs known to be involved in tumor progression were found down-regulated in intestinal group.In addition,only 3 miRNAs were found differentially expressed between GISTs and EGISTs.Conclusion： GISTs and EGISTs have similar miRNA expression patterns related with sites and mutation status;miRNA expression patterns may help to differentiate GISTs at the molecular level.

关 键 词：胃肠道间质瘤 胃肠外间质瘤 微小RNA 基因突变 石蜡组织 

分 类 号：R735[医药卫生—肿瘤] R730.2[医药卫生—临床医学]