Abstract

BackgroundProton pump inhibitor (PPI) medication and surgical fundoplication are used for the control of gastro-oesophageal reflux in patients with Barrett's oesophagus, but differ in their effectiveness for both acid and bile reflux. This might impact on the inflammatory processes that are associated with progression of Barrett's oesophagus to cancer, and this may be evident in the gene expression profile and microRNA expression pattern in Barrett's oesophagus mucosa. We hypothesised that two miRNAs with inflammatory and oncogenic roles, miR-101 and miR-196a, are differentially expressed in Barrett's oesophagus epithelium in patients with reflux treated medically vs. surgically.FindingsMucosal tissue was obtained at endoscopy from patients with Barrett's oesophagus whose reflux was controlled by proton pump inhibitor (PPI) therapy (n = 20) or by fundoplication (n = 19). RNA was extracted and the expression of miR-101 and miR-196a was measured using real-time reverse transcription - polymerase chain reaction. There were no significant differences in miR-101 and miR-196a expression in Barrett's oesophagus epithelium in patients treated by PPI vs. fundoplication (p = 0.768 and 0.211 respectively). Secondary analysis showed a correlation between miR-196a expression and Barrett's oesophagus segment length (p = 0.014).ConclusionThe method of reflux treatment did not influence the expression of miR-101 and miR-196a in Barrett's oesophagus. This data does not provide support to the hypothesis that surgical treatment of reflux better prevents cancer development in Barrett's oesophagus. The association between miR-196a expression and Barrett's oesophagus length is consistent with a tumour promoting role for miR-196a in Barrett's oesophagus.

Highlights

  • Proton pump inhibitor (PPI) medication and surgical fundoplication are used for the control of gastro-oesophageal reflux in patients with Barrett’s oesophagus, but differ in their effectiveness for both acid and bile reflux

  • Treatment of gastro-oesophageal reflux in patients with Barrett’s oesophagus is thought to be important, as oncogenic progression may be associated with inflammation, and inflammation can be minimised by effective control

  • It is can be hypothesised that the distal oesophageal epithelium in patients with PPI treated Barrett’s oesophagus may be more prone to ongoing inflammatory oncogenic stimuli, and this may be evident in the gene expression profile exhibited in the Barrett’s oesophagus epithelium

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Summary

Introduction

Proton pump inhibitor (PPI) medication and surgical fundoplication are used for the control of gastro-oesophageal reflux in patients with Barrett’s oesophagus, but differ in their effectiveness for both acid and bile reflux. This might impact on the inflammatory processes that are associated with progression of Barrett’s oesophagus to cancer, and this may be evident in the gene expression profile and microRNA expression pattern in Barrett’s oesophagus mucosa. Treatment of gastro-oesophageal reflux in patients with Barrett’s oesophagus is thought to be important, as oncogenic progression may be associated with inflammation, and inflammation can be minimised by effective control stimuli, and this may be evident in the gene expression profile exhibited in the Barrett’s oesophagus epithelium. It has recently been reported that levels of pro-inflammatory cytokines, including IL-1b, IL-1a, and IL-8, are elevated in Barrett’s oesophagus epithelium in patients treated with PPI’s, compared with patients treated by fundoplication [6]

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