Evidence map›Paper›PMID 29084829›Full record

Trial reportGut2018

Methylation panel is a diagnostic biomarker for Barrett's oesophagus in endoscopic biopsies and non-endoscopic cytology specimens.

Hamza Chettouh, Oliver Mowforth, Núria Galeano-Dalmau, Navya Bezawada, Caryn Ross-Innes, Shona MacRae, Irene Debiram-Beecham, Maria O'Donovan, Rebecca C Fitzgerald

Open access · hybridAbstract readClinical TrialValidation Study
In one paragraph

Trial report in Gut, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
11.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 100 citations in OpenAlex.

  1. Review
  2. Diagnostic and Prognostic Biomarkers for Barrett's Esophagus.Gastroenterology clinics of North America · 2026
    Review
  3. Emerging Biomarkers for Managing Barrett's Esophagus.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  4. Review
  5. Review
  6. Carcinoma of Esophagus.Journal of gastroenterology and hepatology · 2025
    Review
  7. Review
  8. Observational
  9. Review
  10. Review
  11. Article
  12. Algorithm Training and Testing for a Nonendoscopic Barrett's Esophagus Detection Test in Prospective Multicenter Cohorts.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2024
    Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Hamza ChettouhMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
Oliver MowforthMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
Núria Galeano-DalmauMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
Navya BezawadaMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
Caryn Ross-InnesMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
Shona MacRaeMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
Irene Debiram-BeechamMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
Maria O'DonovanDepartment of Histopathology, Addenbrooke's Hospital, Cambridge, UK.
Rebecca C FitzgeraldMRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
University of Cambridge · GBHutchison/MRC Research Centre · GBAddenbrooke's Hospital · GBMRC Cancer Unit · GB

Funding

Cancer Research UK 12088Cancer Research UK A12088Cancer Research UK C14478/A12088Medical Research Council MC_UU_12022/2
6 · The paper itself

Abstract

objectiveBarrett's oesophagus is a premalignant condition that occurs in the context of gastro-oesophageal reflux. However, most Barrett's cases are undiagnosed because of reliance on endoscopy. We have developed a non-endoscopic tool: the Cytosponge, which when combined with trefoil factor 3 immunohistochemistry, can diagnose Barrett's oesophagus. We investigated whether a quantitative methylation test that is not reliant on histopathological analysis could be used to diagnose Barrett's oesophagus.

designDifferentially methylated genes between Barrett's and normal squamous oesophageal biopsies were identified from whole methylome data and confirmed using MethyLight PCR in biopsy samples of squamous oesophagus, gastric cardia and Barrett's oesophagus. Selected genes were then tested on Cytosponge BEST2 trial samples comprising a pilot cohort (n=20 cases, n=10 controls) and a validation cohort (n=149 cases, n=129 controls).

resultsEighteen genes were differentially methylated in patients with Barrett'soesophagus compared with squamous controls. Hypermethylation of TFPI2, TWIST1, ZNF345 and ZNF569 was confirmed in Barrett's biopsies compared with biopsies from squamous oesophagus and gastric cardia (p<0.05). When tested in Cytosponge samples, these four genes were hypermethylated in patients with Barrett's oesophagus compared with patients with reflux symptoms (p<0.001). The optimum biomarker to diagnose Barrett's oesophagus was TFPI2 with a sensitivity and specificity of 82.2% and 95.7%, respectively.

conclusionTFPI2, TWIST1, ZNF345 and ZNF569 methylation have promise as diagnostic biomarkers for Barrett's oesophagus when used in combination with a simple and cost effective non-endoscopic cell collection device.

Indexed as

AdultAgedBarrett EsophagusBiomarkersBiopsyCytological TechniquesDNA MethylationEsophagoscopyEsophagusFemaleHumansImmunohistochemistryMaleMiddle AgedPolymerase Chain ReactionSensitivity and SpecificityBiomarkersbarrett’sbiomarkercytospongehypermethylationnon-endoscopic cell samplingreflux

Identifiers

PMID29084829
PMCPMC6176521
OpenAlexW2766519221

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.