MicroRNA expression signatures during malignant progression from Barrett's esophagus to esophageal adenocarcinoma.
MicroRNA expression signatures during malignant progression from Barrett's esophagus to esophageal adenocarcinoma.
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DOI：
10.1158/1940-6207.capr-12-0276
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Hawk E
中科院分区：
文献类型：
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作者：
Wu X;Ajani JA;Gu J;Chang DW;Tan W;Hildebrandt MA;Huang M;Wang KK;Hawk E
巴雷特食管（BE）是食管腺癌（EA）的前体病变，其进展遵循顺序分期。然而，低进展率以及预测BE进展的组织学分级的不充分和主观解释需要更客观的生物标志物来改善风险预测。我们使用Taqman实时pcr技术对35个正常上皮（NE）、34个BE和36个EA组织中的754个人类microRNAs （miRNAs）进行了全基因组分析。使用294个中度至高度表达的mirna进行无监督分层聚类，结果显示两组组织明显聚类：NE组与BE/EA组。此外，NE组织中Barrett’s化生（BM，无发育不良）组织的聚集性很好。不同分期的BE组织和EA组织均有分布。不同阶段存在差异表达的mirna。大多数miRNA畸变涉及BE和EA组织的表达上调，最显著的改变发生在BM阶段。已知的肿瘤mirna，如miR-21、miR-25和miR-223，以及肿瘤抑制mirna，包括miR-205、miR-203、let-7c和miR-133a，从BE到EA的表达逐渐改变。我们还鉴定了一些新的mirna，包括miR-301b、miR-618和miR-23b，表达逐渐改变。EA而非BE独有的显著miRNA改变包括miR-375的下调和miR-17-92及其同源簇的5个成员的上调，这可能成为EA发展的有希望的生物标志物。
Barrett’s esophagus (BE) is the precursor lesion of esophageal adenocarcinoma (EA), whose progression follows sequential stages. However, the low progression rate and the inadequacy and subjective interpretation of histological grading in predicting BE progression call for more objective biomarkers that can improve risk prediction. We performed a genome-wide profiling of 754 human microRNAs (miRNAs) in 35 normal epithelium (NE), 34 BE, and 36 EA tissues using Taqman real-time PCR-based profiling. Unsupervised hierarchical clustering using 294 modestly to highly expressed miRNAs showed clear clustering of two groups: NE versus BE/EA tissues. Moreover, there was an excellent clustering of Barrett’s metaplasia (BM, without dysplasia) tissues from NE tissues. However, BE tissues of different stages and EA tissues were interspersed. There were differentially expressed miRNAs at different stages. The majority of miRNA aberrations involved upregulation of expression in BE and EA tissues, with the most dramatic alterations occurring at the BM stage. Known oncomirs, such as miR-21, miR-25 and miR-223, and tumor suppressor miRNAs, including miR-205, miR-203, let-7c, and miR-133a, showed progressively altered expression from BE to EA. We also identified a number of novel miRNAs that showed progressively altered expression, including miR-301b, miR-618, and miR-23b. The significant miRNA alterations that were exclusive to EA but not BE included miR-375 downregulation and upregulation of five members of the miR-17-92 and its homologue clusters, which may become promising biomarkers for EA development.