Validation of an Epigenetic Prognostic Assay to Accurately Risk-Stratify Patients with Barrett’s Esophagus

Sarah E. Laun, Lisa Kann, Jerome Braun, Stacey Gilbert, Daniel Lunz, Francia Pierre, Andrew Kalra, Ke Ma, Hua Ling Tsai, Hao Wang, Simran Jit, Yulan Cheng, Yousra Ahmed, Kenneth K. Wang, Cadman L. Leggett, Ashley Cellini, Olga B. Ioffe, Ali H. Zaidi, Ashten N. Omstead, Blair JobeLouis Korman, Drew Cornish, Pauline Zellenrath, Manon Spaander, Ernst Kuipers, Lorrie Perpetua, Bruce D. Greenwald, Tara Maddala, Stephen J. Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Abstract

INTRODUCTION:
Esophageal adenocarcinoma (EAC) is the second-most lethal cancer in the United States, with Barrett esophagus (BE) being the strongest risk factor. Assessing the future risk of neoplastic progression in patients with BE is difficult; however, high-grade dysplasia (HGD) and early EAC are treatable by endoscopic eradication therapy (EET), with survival rates of 90%. Thus, it would be beneficial to develop a molecular assay to identify high-risk patients, who merit more frequent endoscopic surveillance or EET, as well as low-risk patients, who can avoid EET and undergo less frequent surveillance.

METHODS:
Deidentified endoscopic biopsies were acquired from 240 patients with BE at 6 centers and confirmed as future progressors or nonprogressors. Tissues were analyzed by a set of methylation-specific biomarker assays. Test performance was assessed in an independent validation set using 4 stratification levels: low risks, low-moderate risks, high-moderate risks, and high risks.

RESULTS:
Relative to patients in the low-risk group, high-risk patients were 15.2 times more likely to progress within 5 years to HGD or EAC. For patients in the high-risk category, the average risk of progressing to HGD or EAC within 5 years was 21.5%, 4-fold the BE population prevalence within 5 years, whereas low-risk patients had a progression risk of only 1.85%.

DISCUSSION:
This clinical assay, Esopredict, stratifies future neoplastic progression risk to identify higher-risk patients with BE who can benefit from EET or more frequent surveillance and lower-risk patients who can benefit from reduced surveillance.
Original languageEnglish
Article number3030
JournalAmerican Journal of Gastroenterology
DOIs
Publication statusE-pub ahead of print - 14 Aug 2024

Bibliographical note

Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology

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