MicroRNA expression signatures during malignant progression from Barrett’s esophagus to esophageal adenocarcinoma

摘要

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.