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 Washington & 10 others Jean Wang, Marcia Irene Canto, Achyut K Bhattacharyya, Mark A Nelson, Paul D. Wagner, Yvonne Romero, Kenneth K. Wang, Ziding Feng, Richard E. Sampliner, Stephen J. Meltzer

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)4112-4115
Number of pages4
JournalCancer Research
Volume69
Issue number10
DOIs
StatePublished - May 15 2009

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Barrett Esophagus
Validation Studies
Methylation
Biomarkers
Area Under Curve
ROC Curve
Endoscopy
Real-Time Polymerase Chain Reaction
Adenocarcinoma
Logistic Models
Regression Analysis
Population
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus. / Jin, Zhe; Cheng, Yulan; Gu, Wen; Zheng, Yingye; Sato, Fumiaki; Mori, Yuriko; Olaru, Alexandru V.; Paun, Bogdan C.; Yang, Jian; Kan, Takatsugu; Ito, Tetsuo; Hamilton, James P.; Selaru, Florin M.; Agarwal, Rachana; David, Stefan; Abraham, John M.; Wolfsen, Herbert C.; Wallace, Michael B.; Shaheen, Nicholas J.; Washington, Kay; Wang, Jean; Canto, Marcia Irene; Bhattacharyya, Achyut K; Nelson, Mark A; Wagner, Paul D.; Romero, Yvonne; Wang, Kenneth K.; Feng, Ziding; Sampliner, Richard E.; Meltzer, Stephen J.

In: Cancer Research, Vol. 69, No. 10, 15.05.2009, p. 4112-4115.

Research output: Contribution to journalArticle

Jin, Z, Cheng, Y, Gu, W, Zheng, Y, Sato, F, Mori, Y, Olaru, AV, Paun, BC, Yang, J, Kan, T, Ito, T, Hamilton, JP, Selaru, FM, Agarwal, R, David, S, Abraham, JM, Wolfsen, HC, Wallace, MB, Shaheen, NJ, Washington, K, Wang, J, Canto, MI, Bhattacharyya, AK, Nelson, MA, Wagner, PD, Romero, Y, Wang, KK, Feng, Z, Sampliner, RE & Meltzer, SJ 2009, 'A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus', Cancer Research, vol. 69, no. 10, pp. 4112-4115. https://doi.org/10.1158/0008-5472.CAN-09-0028
Jin, Zhe ; Cheng, Yulan ; Gu, Wen ; Zheng, Yingye ; Sato, Fumiaki ; Mori, Yuriko ; Olaru, Alexandru V. ; Paun, Bogdan C. ; Yang, Jian ; Kan, Takatsugu ; Ito, Tetsuo ; Hamilton, James P. ; Selaru, Florin M. ; Agarwal, Rachana ; David, Stefan ; Abraham, John M. ; Wolfsen, Herbert C. ; Wallace, Michael B. ; Shaheen, Nicholas J. ; Washington, Kay ; Wang, Jean ; Canto, Marcia Irene ; Bhattacharyya, Achyut K ; Nelson, Mark A ; Wagner, Paul D. ; Romero, Yvonne ; Wang, Kenneth K. ; Feng, Ziding ; Sampliner, Richard E. ; Meltzer, Stephen J. / A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus. In: Cancer Research. 2009 ; Vol. 69, No. 10. pp. 4112-4115.
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T1 - A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus

AU - Jin, Zhe

AU - Cheng, Yulan

AU - Gu, Wen

AU - Zheng, Yingye

AU - Sato, Fumiaki

AU - Mori, Yuriko

AU - Olaru, Alexandru V.

AU - Paun, Bogdan C.

AU - Yang, Jian

AU - Kan, Takatsugu

AU - Ito, Tetsuo

AU - Hamilton, James P.

AU - Selaru, Florin M.

AU - Agarwal, Rachana

AU - David, Stefan

AU - Abraham, John M.

AU - Wolfsen, Herbert C.

AU - Wallace, Michael B.

AU - Shaheen, Nicholas J.

AU - Washington, Kay

AU - Wang, Jean

AU - Canto, Marcia Irene

AU - Bhattacharyya, Achyut K

AU - Nelson, Mark A

AU - Wagner, Paul D.

AU - Romero, Yvonne

AU - Wang, Kenneth K.

AU - Feng, Ziding

AU - Sampliner, Richard E.

AU - Meltzer, Stephen J.

PY - 2009/5/15

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N2 - 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.

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