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

Katherine S. Garman, Kouros Owzar, Elizabeth R. Hauser, Kristen Westfall, Blair R. Anderson, Rhonda F. Souza, Anna Mae Diehl, Dawn Provenzale, Nicholas J. Shaheen

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3178-3188
Number of pages11
JournalDigestive Diseases and Sciences
Volume58
Issue number11
DOIs
StatePublished - Nov 2013

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Barrett Esophagus
Esophageal Neoplasms
MicroRNAs
Epithelium
Adenocarcinoma
Real-Time Polymerase Chain Reaction
Esophagus
Cell Line
Microarray Analysis

Keywords

  • Barrett esophagus
  • Esophageal neoplasms
  • Microarray analysis
  • microRNAs

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

MicroRNA expression differentiates squamous epithelium from barrett's esophagus and esophageal cancer. / Garman, Katherine S.; Owzar, Kouros; Hauser, Elizabeth R.; Westfall, Kristen; Anderson, Blair R.; Souza, Rhonda F.; Diehl, Anna Mae; Provenzale, Dawn; Shaheen, Nicholas J.

In: Digestive Diseases and Sciences, Vol. 58, No. 11, 11.2013, p. 3178-3188.

Research output: Contribution to journalArticle

Garman, KS, Owzar, K, Hauser, ER, Westfall, K, Anderson, BR, Souza, RF, Diehl, AM, Provenzale, D & Shaheen, NJ 2013, 'MicroRNA expression differentiates squamous epithelium from barrett's esophagus and esophageal cancer', Digestive Diseases and Sciences, vol. 58, no. 11, pp. 3178-3188. https://doi.org/10.1007/s10620-013-2806-7
Garman, Katherine S. ; Owzar, Kouros ; Hauser, Elizabeth R. ; Westfall, Kristen ; Anderson, Blair R. ; Souza, Rhonda F. ; Diehl, Anna Mae ; Provenzale, Dawn ; Shaheen, Nicholas J. / MicroRNA expression differentiates squamous epithelium from barrett's esophagus and esophageal cancer. In: Digestive Diseases and Sciences. 2013 ; Vol. 58, No. 11. pp. 3178-3188.
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T1 - MicroRNA expression differentiates squamous epithelium from barrett's esophagus and esophageal cancer

AU - Garman, Katherine S.

AU - Owzar, Kouros

AU - Hauser, Elizabeth R.

AU - Westfall, Kristen

AU - Anderson, Blair R.

AU - Souza, Rhonda F.

AU - Diehl, Anna Mae

AU - Provenzale, Dawn

AU - Shaheen, Nicholas J.

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

KW - Barrett esophagus

KW - Esophageal neoplasms

KW - Microarray analysis

KW - microRNAs

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