A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus
Year: 2020
Type: article
Study design: Observational Study
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 8 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 (NPs) and 50 progressors (Ps) using real-time quantitative methylation-specific PCR. Ps were significantly older than NPs (70.6 vs. 62.5 years, p < 0.001). We evaluated a linear combination of the 8 markers, using coefficients from a multivariate logistic regression analysis. Areas under the ROC curve (AUCs) were high in the 2-, 4-year and combined data models (0.843, 0.829 and 0.840; p<0.001, p<0.001 and p<0.001, respectively). In addition, even after rigorous overfitting correction, the incremental AUCs contributed by panels based on the 8 markers plus age vs. age alone were substantial (Δ-AUC = 0.152, 0.114 and 0.118, respectively) in all three 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.
DOI: 10.17615/tz8h-dn40
Authors: Hamilton, James P., Paun, Bogdan C., Mori, Yuriko, Olaru, Alexandru V., Romero, Yvonne, Cheng, Yulan, Meltzer, Stephen J., Agarwal, Rachana, Ito, Tetsuo, Sato, Fumiaki, Jin, Zhe, Canto, Marcia Irene, Yang, Jian, David, Stefan, Abraham, John M., Zheng, Yingye, Kan, Takatsugu, Shaheen, Nicholas J., Wagner, Paul D., Feng, Ziding, Washington, Kay, Gu, Wen, Selaru, Florin M., Sampliner, Richard E., Wang, Jean, Bhattacharyya, Achyut, Wang, Kenneth K., Wolfsen, Herbert C., Wallace, Michael B., Nelson, Mark A.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4300103426