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Discovery of Methylated DNA Biomarkers for Potential Nonendoscopic Detection of Barrett's Esophagus and Esophageal Adenocarcinoma
Journal article   Open access   Peer reviewed

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, …
The American journal of gastroenterology, v 120(10), pp 2268-2279
Oct 2025
DOI: https://doi.org/10.14309/ajg.0000000000003323
PMID: 39819761
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://pure.eur.nl/en/publications/79cffb42-e642-4913-9b65-46faad1ee43aView
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Abstract

Adenocarcinoma - diagnosis Adenocarcinoma - genetics Adenocarcinoma - pathology Aged Barrett Esophagus - diagnosis Barrett Esophagus - genetics Barrett Esophagus - pathology Biomarkers, Tumor - genetics Case-Control Studies DNA Methylation Esophageal Neoplasms - diagnosis Esophageal Neoplasms - genetics Esophageal Neoplasms - pathology Esophagus - pathology Female Humans Male Middle Aged Precancerous Conditions - diagnosis Precancerous Conditions - genetics Precancerous Conditions - pathology
We 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]). We 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. Twelve 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. 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.

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7 citations in Web of Science
3 citations in Scopus

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Web of Science research areas
Gastroenterology & Hepatology
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