MicroRNA expression signatures in Barrett's esophagus and esophageal adenocarcinoma.
OBJECTIVE
Esophageal adenocarcinoma is a highly aggressive malignancy that frequently develops from Barrett's esophagus, a premalignant pathologic change occurring in the lower end of the esophagus. Identifying Barrett's esophagus patients at high risk of malignant transformation is essential to the prevention of esophageal adenocarcinoma. Although microRNA (miRNA) expression signatures have been associated with the etiology and prognosis of several types of cancers, their roles in the development of esophageal adenocarcinoma have not been extensively evaluated.


METHODS
In this study, we analyzed the expression patterns of 470 human miRNAs using Agilent miRNA microarray in 32 disease/normal-paired tissues from 16 patients diagnosed with Barrett's esophagus of either low- or high-grade dysplasia, or esophageal adenocarcinoma.


RESULTS
Using unsupervised hierarchical clustering and class comparison analyses, we found that miRNA expression profiles in tissues of Barrett's esophagus with high-grade dysplasia were significantly different from their corresponding normal tissues. Similar findings were observed for esophageal adenocarcinoma, but not for Barrett's esophagus with low-grade dysplasia. The expression patterns of selected miRNAs were further validated using quantitative reverse transcription real-time PCR in an independent set of 75 pairs of disease/normal tissues. Finally, we identified several miRNAs that were involved in the progressions from low grade-dysplasia Barrett's esophagus to esophageal adenocarcinoma.


CONCLUSIONS
We showed that miRNAs were involved in the development and progression of esophageal adenocarcinoma. The identified significant miRNAs that may become potential targets for early detection, chemoprevention, and treatment of esophageal cancer.
Yang
Hushan
H
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Gu
Jian
J
Wang
Kenneth K
KK
Zhang
Wei
W
Xing
Jinliang
J
Chen
Zhinan
Z
Ajani
Jaffer A
JA
Wu
Xifeng
X
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000175:diagnosis / Q000235:genetics*; D016000:Cluster Analysis; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000235:genetics*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs