Document Detail

A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus.
MedLine Citation:
PMID:  19435894     Owner:  NLM     Status:  MEDLINE    
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 methylation-specific 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 (Delta-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.
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; Jean 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
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-12
Journal Detail:
Title:  Cancer research     Volume:  69     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-18     Completed Date:  2009-07-08     Revised Date:  2014-04-30    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4112-5     Citation Subset:  IM    
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MeSH Terms
Age Factors
Barrett Esophagus / pathology*,  physiopathology
Biological Markers / blood,  metabolism
Core Binding Factor Alpha 3 Subunit / genetics
Disease Progression
Double-Blind Method
Esophageal Neoplasms / epidemiology*,  pathology
Gene Expression Regulation
Gene Expression Regulation, Neoplastic
Membrane Proteins / genetics
Neoplasm Proteins / genetics
Polymerase Chain Reaction
Predictive Value of Tests
Promoter Regions, Genetic
ROC Curve
Reproducibility of Results
Risk Assessment
Grant Support
CA001808/CA/NCI NIH HHS; CA062924/CA/NCI NIH HHS; CA085069/CA/NCI NIH HHS; CA106763/CA/NCI NIH HHS; CA106991/CA/NCI NIH HHS; CA95060/CA/NCI NIH HHS; R01 CA001808/CA/NCI NIH HHS; R01 CA001808-05/CA/NCI NIH HHS; R01 CA133012/CA/NCI NIH HHS; R01 DK087454/DK/NIDDK NIH HHS; R21 CA106763/CA/NCI NIH HHS; R21 CA106763-02/CA/NCI NIH HHS; T32 DK067872/DK/NIDDK NIH HHS; U01 CA085069/CA/NCI NIH HHS; U01 CA085069-08/CA/NCI NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/Core Binding Factor Alpha 3 Subunit; 0/Membrane Proteins; 0/Neoplasm Proteins; 0/P16 protein, human; 0/Runx3 protein, human; 0/TMEFF2 protein, human

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