| A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus. | |
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MedLine Citation:
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PMID: 19435894 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-12 |
Journal Detail:
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Title: Cancer research Volume: 69 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-18 Completed Date: 2009-07-08 Revised Date: 2013-05-10 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 4112-5 Citation Subset: IM |
Affiliation:
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Gastroenterology Division, Johns Hopkins University, Baltimore, MD 21287, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Age Factors Barrett Esophagus / pathology*, physiopathology Biological Markers / blood, metabolism Core Binding Factor Alpha 3 Subunit / genetics Disease Progression Double-Blind Method Endoscopy Esophageal Neoplasms / epidemiology*, pathology Gene Expression Regulation Gene Expression Regulation, Neoplastic Humans 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 | |
ID/Acronym/Agency:
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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; U01 CA085069/CA/NCI NIH HHS; U01 CA085069-08/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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