Evidence map›Paper›PMID 39819761›Full record

ArticleThe American journal of gastroenterology2025

Discovery of Methylated DNA Biomarkers for Potential Nonendoscopic Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

Andrew Kalra, Ke Ma, Yulan Cheng, Hua-Ling Tsai, Hao Wang, Leslie Cope, Yifan Yang, Daniel Lunz, Sarah Laun, Lisa Kann and 30 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Screening for Barrett's esophagus and esophageal adenocarcinoma: recent advances and next steps.Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus · 2026
    Review
  2. Review
  3. Diagnostic and Prognostic Biomarkers for Barrett's Esophagus.Gastroenterology clinics of North America · 2026
    Review
  4. Emerging Biomarkers for Managing Barrett's Esophagus.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  5. Review
  6. Article
  7. 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

40 authors.

Andrew KalraDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0001-8338-019
Ke MaDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yulan ChengDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hua-Ling TsaiDepartment of Medicine, Division of Gastroenterology and Hepatology, Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA.ORCID 0000-0001-8388-6297
Hao WangDepartment of Medicine, Division of Gastroenterology and Hepatology, Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA.ORCID 0000-0001-6489-6940
Leslie CopeDivision of Biostatistics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yifan YangDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Daniel LunzPrevise, Baltimore, Maryland, USA.
Sarah LaunPrevise, Baltimore, Maryland, USA.ORCID 0000-0002-6783-315
Lisa KannPrevise, Baltimore, Maryland, USA.
Simran JitDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yousra AhmedDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Shayan GheshlaghiDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-0193-5591
Alan H TieuDivision of Gastroenterology, Eastern Virginia Medical School, Norfolk, Virginia, USA.
Vincent CastilloDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0009-0007-3258-5882
Russell HalesDepartment of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland, USA.
Josephine FelicianoJohns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
Vincent LamJohns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.ORCID 0000-0002-1319-2588
Kristin MarroneJohns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
Ken HuiDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-4174-4802
Michelle MaDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Robert HughesDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-4182-9136
Venkata AkshintalaDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-8909-1951
Kathy Bull-HenryDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jinny HaDivision of Thoracic Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, USA.ORCID 0000-0003-1044-8186
Karim BoudadiJohns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
Zacharia H FodaDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-3591-8482
Richard BattaforanoDivision of Thoracic Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Vikesh K SinghDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mouen KhashabDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Eun Ji ShinDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0003-0624-8149
Olaya BrewerDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0001-6338-3801
Saowanee NgamruengphongDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Rachel GansterAllegheny Health Network, Pittsburgh, Pennsylvania, USA.
Blair A JobeAllegheny Health Network, Pittsburgh, Pennsylvania, USA.
Shahin AyaziAllegheny Health Network, Pittsburgh, Pennsylvania, USA.
Pauline ZellenrathDivision of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID 0009-0003-4902-5663
Manon SpaanderDivision of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0002-9103-9757
Ali H ZaidiAllegheny Health Network, Pittsburgh, Pennsylvania, USA.ORCID 0000-0002-5463-2252
Stephen J MeltzerDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-9131-1052

Funding

Academic-Industrial Partnership for Non-invasive Barrett's Esophagus DetectionR01DK118250 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J · 2018 to 2022
$3.8M
Facile screening for esophageal cancer in LMICsUH3CA211457 · NCI · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J, WANG, TZA-HUEI JEFF · 2019 to 2021
$2.8M
Academic-Industrial Partnership for Barrett's Esophagus Detection and Risk AssessmentR01CA287294 · NCI · JOHNS HOPKINS UNIVERSITY · PI Stephen J Meltzer · 2024 to 2026
$2.3M
Facile screening for esophageal cancer in LMICsUG3CA211457 · NCI · JOHNS HOPKINS UNIVERSITY · PI MELTZER, STEPHEN J, WANG, TZA-HUEI JEFF · 2017 to 2018
$861k
Division of Cancer Prevention, National Cancer Institute CA211457Division of Cancer Prevention, National Cancer Institute CA287294Division of Cancer Prevention, National Cancer Institute DK118250National Institute of Diabetes, Digestive and Kidney Diseases DK118250NCI NIH HHS R01 CA287294NCI NIH HHS UG3 CA211457NCI NIH HHS UH3 CA211457NIDDK NIH HHS R01 DK118250
6 · The paper itself

Abstract

introductionWe sought to develop a minimally invasive, robust, accessible nonendoscopic strategy to diagnose Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), and its immediate precursor lesion, high-grade dysplasia (HGD) based on methylated DNA biomarkers applied to a retrievable sponge-capsule device in a cohort representative of the BE population (i.e., mostly short-segment, nondysplastic BE [NDBE]).

methodsWe identified 12 candidate methylation markers to distinguish normal vs abnormal esophagus. These 12 markers were first assayed in 21-paired matched NDBE-normal esophageal tissues, then assessed in a case-control study of 234 esophageal samples collected using a sponge-capsule device. A classification algorithm was developed using the least absolute shrinkage and selection operator in a 199-patient training set and tested in an independent 35-patient test set.

resultsTwelve markers ( A1BG , C9orf50 , cg00720137 , FLI1 , GRAMD1B , HOXB13 , IRF4 , KCNQ3 , NTNG1 , SPX , TBC1D30 , and USP44 ) were significantly hypermethylated (i.e., all P < 0.05) in BE vs matched normal esophageal biopsies. A discriminatory 3-gene least absolute shrinkage and selection operator panel ( USP44 , TBC1D30 , and NELL1 ), adjusted for age and sex, accurately distinguished HGD or EAC from normal control patients in both training (area under the receiver operating characteristic curve [AUC] 0.911, 95% confidence interval [CI] 0.863-0.959) and test (AUC 0.969, 95% CI 0.911-1.00) sets. In normal vs NDBE/LGD/HGD/EAC patients, this algorithm exhibited AUCs of 0.862 (95% CI 0.812-0.912) and 0.864 (95% CI 0.745-0.982) in training and test sets, respectively. In normal vs NDBE patients, the algorithm yielded AUCs of 0.819 (95% CI 0.748-0.889) and 0.776 (95% CI 0.583-0.968) in training and test sets, respectively. DISCUSSION: This discriminatory biomarker panel algorithm exemplifies a practical nonendoscopic strategy to diagnose BE, HGD, and EAC using a minimally invasive sponge-capsule device coupled with DNA methylation markers.

Indexed as

AdenocarcinomaBarrett EsophagusBiomarkers, TumorDNA MethylationEsophageal NeoplasmsPrecancerous ConditionsAgedCase-Control StudiesEsophagusFemaleHumansMaleMiddle AgedBiomarkers, TumorBarrett's esophagusesophageal adenocarcinomaleast absolute shrinkage and selection operatormethylated DNA biomarkerssponge-on-a-string device

Identifiers

PMID39819761
PMCPMC12870103

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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.