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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 differences of microRNA (miRNA) expression profiles between gastrointestinal stromal tumors (GISTs) and extra-gastrointestinal stromal tumors (EGISTs) in primary gastrointestinal tract, Location, type of mutation and other factors. Methods: Eight paraffin samples (5 cases of GISTs and 3 cases of EGISTs) from Xijing Hospital were collected and analyzed by using Agilent miRNA microarrays (866 microRNAs). At the same time direct sequencing by PCR amplification, a clear eight cases of gene mutation types. Results: The results of non-supervised hierarchical cluster analysis showed that 8 samples were divided into 3 clusters, 1 GIST with the same mutation type and 1 EGIST with the same mutation type, 2 GISTs with 2 gastric clusters, The remaining 4 cases (2 cases of intestinal GISTs and 2 cases of EGISTs) constitute the third cluster. Five cases of GISTs were divided into two groups according to the site (stomach and intestine). Three EGISTs were added into groups with similar miRNA phenotypes. Twelve miRNAs were found to be significantly different between the two groups. The majority of predicted target genes were involved in KIT / PDGFRA signal transduction, five of which were significantly downregulated in the gut group, some of which have been reported to correlate with tumor progression. Comparing the expression profiles of GISTs and EGISTs, it was found that there were only statistically significant differences in the expression of three miRNAs. CONCLUSIONS: The miRNA phenotypes of GISTs and EGISTs are similar, which are closely related to tumor location and mutation type. Therefore, the analysis of miRNA phenotype may be helpful for the classification of GISTs at the molecular level.