MicroRNA expression differentiates squamous epithelium from barrett's esophagus and esophageal cancer

Published

Journal Article

Background: Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed. Aim: We sought to assess whether differential expression of microRNAs could discriminate between squamous epithelium, Barrett's esophagus (BE), and EAC. Methods: We analyzed microRNA expression in a discovery cohort of human endoscopic biopsy samples from 36 patients representing normal squamous esophagus (n = 11), BE (n = 14), and high-grade dysplasia/EAC (n = 11). RNA was assessed using microarrays representing 847 human microRNAs followed by quantitative real-time polymerase chain reaction (qRT-PCR) verification of nine microRNAs. In a second cohort (n = 18), qRT-PCR validation of five miRNAs was performed. Expression of 59 microRNAs associated with BE/EAC in the literature was assessed in our training cohort. Known esophageal cell lines were used to compare miRNA expression to tissue miRNAs. Results: After controlling for multiple comparisons, we found 34 miRNAs differentially expressed between squamous esophagus and BE/EAC by microarray analysis. However, miRNA expression did not reliably differentiate non-dysplastic BE from EAC. In the validation cohort, all five microRNAs selected for qRT-PCR validation differentiated between squamous samples and BE/EAC. Microarray results supported 14 of the previously reported microRNAs associated with BE/EAC in the literature. Cell lines did not generally reflect miRNA expression found in vivo. Conclusions: These data indicate that miRNAs differ between squamous esophageal epithelium and BE/EAC, but do not distinguish between BE and EAC. We suggest prospective evaluation of miRNAs in patients at high risk for EAC. © 2013 Springer Science+Business Media New York.

Full Text

Duke Authors

Cited Authors

  • Garman, KS; Owzar, K; Hauser, ER; Westfall, K; Anderson, BR; Souza, RF; Diehl, AM; Provenzale, D; Shaheen, NJ

Published Date

  • November 1, 2013

Published In

Volume / Issue

  • 58 / 11

Start / End Page

  • 3178 - 3188

Electronic International Standard Serial Number (EISSN)

  • 1573-2568

International Standard Serial Number (ISSN)

  • 0163-2116

Digital Object Identifier (DOI)

  • 10.1007/s10620-013-2806-7

Citation Source

  • Scopus