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Barrett\u2019s oesophagus (BO) is a precursor to OAC, and progression occurs in a stepwise fashion, although the annual risk of progression is relatively low. The incidence of both BO and OAC have been increasing in the Western world. At present, guidelines advise that patients with BO should undergo regular endoscopic surveillance with biopsies, with the degree of dysplasia on biopsy being used to guide further management. However, there are potential disadvantages of this surveillance approach. For example, it is invasive and expensive, and there is interobserver variability between pathologists in the assessment of dysplasia. There is an urgent clinical need for new approaches to identify which patients with BO are at high risk of progression. Biomarkers could potentially be used to risk-stratify patients with BO. Epigenetic changes can occur early in the neoplastic progression of BO, making them attractive for use as potential biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review will be performed to investigate whether epigenetic biomarkers, including DNA methylation, histone modification, and non-coding RNAs, can predict the risk of progression of patients with BO to high-grade dysplasia or OAC. The electronic databases Ovid MEDLINE, Embase, and Web of Science Core Collection will be searched for terms relating to biomarkers, methylation, epigenetics, BO, and OAC. Observational (case-control, retrospective cohort, and prospective cohort) studies and interventional studies will be eligible for inclusion. Studies will be screened independently by two reviewers, and relevant data will be extracted from eligible studies. The risk of bias will be assessed for each study. Random effects meta-analyses will be carried out if possible, otherwise a synthesis without meta-analysis will be performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This systematic review aims to assess whether epigenetic biomarkers can predict progression of BO to OAC. This is an important clinical question, with national gastroenterology societies advising that risk stratification biomarkers could significantly improve the care of patients with BO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>This systematic review protocol has been registered in PROSPERO (international prospective register of systematic reviews), with registration number CRD42024509643.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13643-026-03256-0","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:33:53Z","timestamp":1783474433000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic biomarkers and the progression of Barrett\u2019s oesophagus to oesophageal adenocarcinoma: a systematic review protocol"],"prefix":"10.1186","volume":"15","author":[{"given":"David N.","family":"Johnston","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen G.","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Jayne","family":"McKnight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Turkington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"issue":"1","key":"3256_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1136\/gutjnl-2013-305372","volume":"63","author":"RC Fitzgerald","year":"2014","unstructured":"Fitzgerald RC, Di Pietro M, Ragunath K, Ang Y, Kang JY, Watson P, et al. 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