Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features

Fumiaki Sato, Zhe Jin, Karsten Schulmann, Jean Wang, Bruce D. Greenwald, Tetsuo Ito, Takatsugu Kan, James P. Hamilton, Jian Yang, Bogdan Paun, Stefan David, Alexandru Olaru, Yulan Cheng, Yuriko Mori, John M. Abraham, Harris G. Yfantis, Tsung Teh Wu, Mary B. Fredericksen, Kenneth Ke Ning Wang, Marcia CantoYvonne Romero, Ziding Feng, Stephen J. Meltzer

Research output: Contribution to journalArticle

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Abstract

Background: Barrett's esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barrett's esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barrett's esophagus. Moreover. high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency. Methods and Findings: We defined high-grade dysplasia as endpoint of progression, and Barrett's esophagus progressor patients as Barrett's esophagus patients with either no dysplasia or low-grade dysplasia who later developed high-grade dysplasia or esophageal adenocarcinoma. We analyzed 4 epigenetic and 3 clinical parameters in 118 Barretts esophagus tissues obtained from 35 progressor and 27 non-progressor Barrett's esophagus patients from Baltimore Veterans Affairs Maryland Health Care Systems and Mayo Clinic. Based on 2-year and 4-year prediction models using linear discriminant analysis (area under the receiver-operator characteristic (ROC) curve: 0.8386 and 0.79110, respectively), Barrett's esophagus specimens were stratified into high-risk (HR), intermediate-risk (IR) or low-risk (LR) groups. This 3-tiered stratification method retained both he high specificity of the 2-year model and the high sensitivity of the 4-year model. Progression-free survivals differed significantly among the 3 risk groups, with p=0.0022 (HR vs. IR) and p<0.0001 (HR or IR vs. LR). Incremental value analyses demonstrated that the number of methylated genes contributed most influentially to prediction accuracy. Conclusions: This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett's esophagus surveillance accuracy and efficiency.

Original languageEnglish (US)
Article numbere1890
JournalPLoS One
Volume3
Issue number4
DOIs
StatePublished - Apr 2 2008

Fingerprint

Barrett Esophagus
esophagus
Epigenomics
epigenetics
adenocarcinoma
risk groups
Adenocarcinoma
monitoring
veterans
prediction
operator regions
Baltimore
endpoints
Discriminant Analysis
Veterans
Discriminant analysis
discriminant analysis
health services
risk assessment
Health care

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sato, F., Jin, Z., Schulmann, K., Wang, J., Greenwald, B. D., Ito, T., ... Meltzer, S. J. (2008). Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features. PLoS One, 3(4), [e1890]. https://doi.org/10.1371/journal.pone.0001890

Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features. / Sato, Fumiaki; Jin, Zhe; Schulmann, Karsten; Wang, Jean; Greenwald, Bruce D.; Ito, Tetsuo; Kan, Takatsugu; Hamilton, James P.; Yang, Jian; Paun, Bogdan; David, Stefan; Olaru, Alexandru; Cheng, Yulan; Mori, Yuriko; Abraham, John M.; Yfantis, Harris G.; Wu, Tsung Teh; Fredericksen, Mary B.; Wang, Kenneth Ke Ning; Canto, Marcia; Romero, Yvonne; Feng, Ziding; Meltzer, Stephen J.

In: PLoS One, Vol. 3, No. 4, e1890, 02.04.2008.

Research output: Contribution to journalArticle

Sato, F, Jin, Z, Schulmann, K, Wang, J, Greenwald, BD, Ito, T, Kan, T, Hamilton, JP, Yang, J, Paun, B, David, S, Olaru, A, Cheng, Y, Mori, Y, Abraham, JM, Yfantis, HG, Wu, TT, Fredericksen, MB, Wang, KKN, Canto, M, Romero, Y, Feng, Z & Meltzer, SJ 2008, 'Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features', PLoS One, vol. 3, no. 4, e1890. https://doi.org/10.1371/journal.pone.0001890
Sato, Fumiaki ; Jin, Zhe ; Schulmann, Karsten ; Wang, Jean ; Greenwald, Bruce D. ; Ito, Tetsuo ; Kan, Takatsugu ; Hamilton, James P. ; Yang, Jian ; Paun, Bogdan ; David, Stefan ; Olaru, Alexandru ; Cheng, Yulan ; Mori, Yuriko ; Abraham, John M. ; Yfantis, Harris G. ; Wu, Tsung Teh ; Fredericksen, Mary B. ; Wang, Kenneth Ke Ning ; Canto, Marcia ; Romero, Yvonne ; Feng, Ziding ; Meltzer, Stephen J. / Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features. In: PLoS One. 2008 ; Vol. 3, No. 4.
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AU - Sato, Fumiaki

AU - Jin, Zhe

AU - Schulmann, Karsten

AU - Wang, Jean

AU - Greenwald, Bruce D.

AU - Ito, Tetsuo

AU - Kan, Takatsugu

AU - Hamilton, James P.

AU - Yang, Jian

AU - Paun, Bogdan

AU - David, Stefan

AU - Olaru, Alexandru

AU - Cheng, Yulan

AU - Mori, Yuriko

AU - Abraham, John M.

AU - Yfantis, Harris G.

AU - Wu, Tsung Teh

AU - Fredericksen, Mary B.

AU - Wang, Kenneth Ke Ning

AU - Canto, Marcia

AU - Romero, Yvonne

AU - Feng, Ziding

AU - Meltzer, Stephen J.

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N2 - Background: Barrett's esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barrett's esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barrett's esophagus. Moreover. high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency. Methods and Findings: We defined high-grade dysplasia as endpoint of progression, and Barrett's esophagus progressor patients as Barrett's esophagus patients with either no dysplasia or low-grade dysplasia who later developed high-grade dysplasia or esophageal adenocarcinoma. We analyzed 4 epigenetic and 3 clinical parameters in 118 Barretts esophagus tissues obtained from 35 progressor and 27 non-progressor Barrett's esophagus patients from Baltimore Veterans Affairs Maryland Health Care Systems and Mayo Clinic. Based on 2-year and 4-year prediction models using linear discriminant analysis (area under the receiver-operator characteristic (ROC) curve: 0.8386 and 0.79110, respectively), Barrett's esophagus specimens were stratified into high-risk (HR), intermediate-risk (IR) or low-risk (LR) groups. This 3-tiered stratification method retained both he high specificity of the 2-year model and the high sensitivity of the 4-year model. Progression-free survivals differed significantly among the 3 risk groups, with p=0.0022 (HR vs. IR) and p<0.0001 (HR or IR vs. LR). Incremental value analyses demonstrated that the number of methylated genes contributed most influentially to prediction accuracy. Conclusions: This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett's esophagus surveillance accuracy and efficiency.

AB - Background: Barrett's esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barrett's esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barrett's esophagus. Moreover. high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency. Methods and Findings: We defined high-grade dysplasia as endpoint of progression, and Barrett's esophagus progressor patients as Barrett's esophagus patients with either no dysplasia or low-grade dysplasia who later developed high-grade dysplasia or esophageal adenocarcinoma. We analyzed 4 epigenetic and 3 clinical parameters in 118 Barretts esophagus tissues obtained from 35 progressor and 27 non-progressor Barrett's esophagus patients from Baltimore Veterans Affairs Maryland Health Care Systems and Mayo Clinic. Based on 2-year and 4-year prediction models using linear discriminant analysis (area under the receiver-operator characteristic (ROC) curve: 0.8386 and 0.79110, respectively), Barrett's esophagus specimens were stratified into high-risk (HR), intermediate-risk (IR) or low-risk (LR) groups. This 3-tiered stratification method retained both he high specificity of the 2-year model and the high sensitivity of the 4-year model. Progression-free survivals differed significantly among the 3 risk groups, with p=0.0022 (HR vs. IR) and p<0.0001 (HR or IR vs. LR). Incremental value analyses demonstrated that the number of methylated genes contributed most influentially to prediction accuracy. Conclusions: This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett's esophagus surveillance accuracy and efficiency.

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