Epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma: a systematic review protocol.

Introduction: Barrett's oesophagus (BO), a metaplastic condition affecting the lower oesophagus due to long-standing gastro-oesophageal reflux and chronic inflammation, is a precursor lesion for oesophageal adenocarcinoma (OADC). There is no clinical test to predict which patients with BO will progress to OADC. The British Society of Gastroenterology recommends endoscopic surveillance of patients with BO. Epigenetic changes have been well characterised in the neoplastic progression of ulcerative colitis to colonic carcinoma, another gastrointestinal cancer associated with chronic inflammation. This systematic review protocol aims to identify and evaluate studies which examine epigenetic biomarkers in BO and their association with progression to OADC. Methods and analysis: All prospective and retrospective primary studies, and existing systematic reviews investigating epigenetic markers including DNA methylation, histone modification, chromatin remodelling, micro and non-coding RNAs of all types will be eligible for inclusion. Eligible patients are those over the age of 18 with BO, BO with dysplasia, OADC or unspecified oesophageal cancer. A comprehensive search of bibliographic databases using combinations of text and index words relating to the population, prognostic markers and outcome will be undertaken with no language restrictions. Results will be screened by 2 independent reviewers and data extracted using a standardised proforma. The quality and risk of bias of individual studies will be assessed using the Quality in Prognostic Studies (QUIPS) tool. A narrative synthesis of all evidence will be performed with key findings tabulated. Meta-analysis will be considered where studies and reported outcomes are considered sufficiently homogeneous, both clinically and methodologically. Findings will be interpreted in the context of the quality of included studies. The systematic review will be reported according to PRISMA guidelines. Ethics and dissemination: This is a systematic review of completed studies and no ethical approval is required. Findings from the full systematic review will be submitted for publication and presentation at national and international conferences which will inform future research on risk stratification in patients with BO.