A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus

Zhe Jin, Yulan Cheng, Wen Gu, Yingye Zheng, Fumiaki Sato, Yuriko Mori, Alexandru V. Olaru, Bogdan C. Paun, Jian Yang, Takatsugu Kan, Tetsuo Ito, James P. Hamilton, Florin M. Selaru, Rachana Agarwal, Stefan David, John M. Abraham, Herbert C. Wolfsen, Michael B. Wallace, Nicholas J. Shaheen, Kay WashingtonJean Wang, Marcia Irene Canto, Achyut Bhattacharyya, Mark A. Nelson, Paul D. Wagner, Yvonne Romero, Kenneth K. Wang, Ziding Feng, Richard E. Sampliner, Stephen J. Meltzer

Research output: Contribution to journalArticlepeer-review

184 Scopus citations


Esophageal adenocarcinoma risk in Barrett's esophagus (BE) is increased 30- to 125-fold versus the general population. Among all BE patients, however, neoplastic progression occurs only once per 200 patient-years. Molecular biomarkers are therefore needed to risk-stratify patients for more efficient surveillance endoscopy and to improve the early detection of progression. We therefore performed a retrospective, multicenter, double-blinded validation study of eight BE progression prediction methylation biomarkers. Progression or nonprogression were determined at 2 years (tier 1) and 4 years (tier 2). Methylation was assayed in 145 nonprogressors and 50 progressors using real-time quantitative methylationspecific PCR. Progressors were significantly older than nonprogressors (70.6 versus 62.5 years; P < 0.001). We evaluated a linear combination of the eight markers, using coefficients from a multivariate logistic regression analysis. Areas under the ROC curve (AUC) were high in the 2-year, 4-year, and combined data models (0.843, 0.829, and 0.840; P < 0.001, <0.001, and <0.001, respectively). In addition, even after rigorous overfitting correction, the incremental AUCs contributed by panels based on the 8 markers plus age versus age alone were substantial (Δ-AUC = 0.152, 0.114, and 0.118, respectively) in all 3 models. A methylation biomarker-based panel to predict neoplastic progression in BE has potential clinical value in improving both the efficiency of surveillance endoscopy and the early detection of neoplasia.

Original languageEnglish
Pages (from-to)4112-4115
Number of pages4
JournalCancer research
Issue number10
StatePublished - May 15 2009


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