Details

Autor(en) / Beteiligte

• ZHE JIN
• YULAN CHENG
• 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
• WEN GU
• JEAN WANG
• IRENE CANT, Marcia
• BHATTACHARYYA, Achyut
• NELSONS, Mark A
• WAGNER, Paul D
• ROMERO, Yvonne
• WANG, Kenneth K
• ZIDING FENG
• SAMPLINER, Richard E
• MELTZER, Stephen J
• YINGYE ZHENG
• SATO, Fumiaki
• MORI, Yuriko
• OLARU, Alexandru V
• PAN, Bogdan C
• JIAN YANG
• KAN, Takatsugu

Titel

A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus

Ist Teil von

• Cancer research (Chicago, Ill.), 2009-05, Vol.69 (10), p.4112-4115

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.