MicroRNA expression differentiates squamous epithelium from Barrett's esophagus and esophageal cancer - PubMed (original) (raw)

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

Katherine S Garman et al. Dig Dis Sci. 2013 Nov.

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.

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Figures

Figure 1

Figure 1

This flow diagram represents the steps in the analysis using the discovery cohort and a separate validation cohort. Several steps we involved as the initial set of 847 miRNA probe sets from the microarray was narrowed to a list of five miRNAs for validation.

Figure 2

Figure 2

In this figure, the vertical axis represents expression by microarray analysis and the horizontal access represents the delta CT values for each of the nine miRNA selected for qRT-PCR verification of microarray results. This figure provides information on direction of expression by tissue type for both the microarray and PCR platforms. Blue represents squamous samples, green represent BE, while red represents EAC. miR-889, miR-487b, miR-30b and miR-21 increased in BE compared to squamous. miR-27a, miR-92a, miR-27b, miR-193b and miR-149 decreased in BE compared to squamous. The figure also demonstrates concordance between microarray and qRT-PCR results (high concordance appears as a diagonal line). In general, the miRNA expression differentiated squamous tissue from BE/EAC, but not BE from EAC.

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