MicroRNA expression profiles of esophageal cancer
MicroRNA expression profiles of esophageal cancer
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DOI：
10.1016/j.jtcvs.2007.08.055
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发表时间：
2008-02-01
影响因子：
6
通讯作者：
Litle, Virginia R.
中科院分区：
文献类型：
--
作者：
Feber, Andrew;Xi, Liqiang;Litle, Virginia R.
目的：通过阵列分析表达的microRNAs为组织和肿瘤分类提供了独特的图谱。本研究的目的是检测Barrett食管癌和食管癌中microRNA的表达，以确定疾病进展的潜在标志物。方法：从35例冷冻标本（腺癌10例，鳞状细胞癌10例，正常上皮9例，Barrett食管5例，高度不典型增生1例）中分离MicroRNA。用Ambion生物阵列（Ambion, Austin, Tex）检测328个人MicroRNA探针的表达。结果：无监督的层次聚类产生了四个主要分支，对应于四个组织学组。一个分支由7个正常上皮样本和1个鳞状细胞癌样本组成。第二支包括7个鳞状细胞癌样本和1个正常上皮样本。第三支包括4份Barrett食管标本和1份鳞状细胞癌标本。第四组包括所有腺癌样本，Barrett食管、正常上皮、鳞状细胞癌和高度不典型增生各1例。主成分分析的监督分类确定正常上皮样本更类似于鳞状细胞癌，而Barrett食管样本更类似于腺癌。样本类型之间的两两比较揭示了可能是肿瘤进展标志物的microrna。mir_ 203和mir_ 205在鳞状细胞癌和腺癌中的表达均比正常上皮低2 ~ 10倍。mir_ 21在两种肿瘤中的表达均比正常上皮高3 ~ 5倍。微阵列预测分析Barrett食管3例，Barrett食管1例，腺癌1例，正常上皮1例。结论：miRNA表达谱可区分食管肿瘤的组织学特征，并可区分正常组织与肿瘤。MicroRNA的表达可能有助于识别Barrett食管进展为腺癌的高风险患者。
Objective: Expression of microRNAs by array analysis provides unique profiles for classifying tissues and tumors. The purpose of our study was to examine microRNA expression in Barrett esophagus and esophageal cancer to identify potential markers for disease progression.Methods: MicroRNA was isolated from 35 frozen specimens (10 adenocarcinoma, 10 squamous cell carcinoma, 9 normal epithelium, 5 Barrett esophagus, and 1 high-grade dysplasia). MicroRNA expression was analyzed with Ambion bioarrays (Ambion, Austin, Tex) containing 328 human microRNA probes.Results: Unsupervised hierarchic clustering resulted in four major branches corresponding with four histologic groups. One branch consisted of 7 normal epithelium samples and 1 squamous cell carcinoma sample. The second branch consisted of 7 squamous cell carcinoma samples and 1 normal epithelium sample. The third branch contained 4 Barrett esophagus samples and 1 squamous cell carcinoma sample. The fourth contained all the adenocarcinoma samples and 1 sample each of Barrett esophagus, normal epithelium, squamous cell carcinoma, and high-grade dysplasia. Supervised classification with principal component analysis determined that the normal epithelium samples were more similar to the squamous cell carcinoma tumors, whereas the Barrett esophagus samples were more similar to adenocarcinoma. Pairwise comparisons between sample types revealed microRNAs that may be markers of tumor progression. Both mir_ 203 and mir_ 205 were expressed 2-to 10-fold lower in squamous cell carcinoma and adenocarcinomas than in normal epithelium. The mir_ 21 expression was 3-to 5-fold higher in both tumors than in normal epithelium. Prediction analysis of microarray classified 3 Barrett esophagus samples as Barrett esophagus, 1 as adenocarcinoma, and 1 as normal epithelium.Conclusion: Expression profiles of miRNA distinguish esophageal tumor histology and can discriminate normal tissue from tumor. MicroRNA expression may prove useful for identifying patients with Barrett esophagus at high risk for progression to adenocarcinoma.