Barrett's esophagus is the precursor lesion of esophageal adenocarcinoma, whose 
progression follows sequential stages. However, the low progression rate and the 
inadequacy and subjective interpretation of histologic grading in predicting 
Barrett's esophagus progression call for more objective biomarkers that can 
improve risk prediction. We conducted a genome-wide profiling of 754 human 
microRNAs (miRNA) in 35 normal epithelium, 34 Barrett's esophagus, and 36 
esophageal adenocarcinoma tissues using TaqMan real-time PCR-based profiling. 
Unsupervised hierarchical clustering using 294 modestly to highly expressed 
miRNAs showed clear clustering of two groups: normal epithelium versus Barrett's 
esophagus/esophageal adenocarcinoma tissues. Moreover, there was an excellent 
clustering of Barrett's metaplasia (without dysplasia) tissues from normal 
epithelium tissues. However, Barrett's esophagus tissues of different stages and 
esophageal adenocarcinoma tissues were interspersed. There were differentially 
expressed miRNAs at different stages. The majority of miRNA aberrations involved 
upregulation of expression in Barrett's esophagus and esophageal adenocarcinoma 
tissues, with the most dramatic alterations occurring at the Barrett's 
metaplasia 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 Barrett's esophagus to esophageal 
adenocarcinoma. 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 esophageal adenocarcinoma 
but not Barrett's esophagus included miR-375 downregulation and upregulation of 
five members of the miR-17-92 and its homologue clusters, which may become 
promising biomarkers for esophageal adenocarcinoma development.