A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus.
A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus.
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DOI：
10.1158/0008-5472.can-09-0028
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发表时间：
2009-05-15
期刊：
影响因子：
11.2
通讯作者：
Meltzer SJ
中科院分区：
文献类型：
--
作者：
Jin Z;Cheng Y;Gu W;Zheng Y;Sato F;Mori Y;Olaru AV;Paun BC;Yang J;Kan T;Ito T;Hamilton JP;Selaru FM;Agarwal R;David S;Abraham JM;Wolfsen HC;Wallace MB;Shaheen NJ;Washington K;Wang J;Canto MI;Bhattacharyya A;Nelson MA;Wagner PD;Romero Y;Wang KK;Feng Z;Sampliner RE;Meltzer SJ
巴雷特食管 (BE) 的食管腺癌风险比一般人群增加 30 至 125 倍。然而，在所有 BE 患者中，每 200 个患者年仅发生一次肿瘤进展。因此，需要分子生物标志物对患者进行风险分层，以便更有效地监测内窥镜检查并改善进展的早期检测。因此，我们对 8 个 BE 进展预测甲基化生物标志物进行了回顾性、多中心、双盲验证研究。进展或不进展在 2 年（第 1 级）和 4 年（第 2 级）时确定。使用实时定量甲基化特异性 PCR 检测 145 个非进展细胞 (NP) 和 50 个进展细胞 (Ps) 的甲基化。 Ps 明显比 NP 年龄大（70.6 岁 vs. 62.5 岁，p < 0.001）。我们使用多元逻辑回归分析的系数评估了 8 个标记的线性组合。 2 年、4 年和组合数据模型中的 ROC 曲线下面积 (AUC) 较高（分别为 0.843、0.829 和 0.840；p<0.001、p<0.001 和 p<0.001）。此外，即使经过严格的过度拟合校正，在所有三个模型中，基于 8 个标记物加上年龄与单独年龄的面板贡献的增量 AUC 仍然很大（Δ-AUC 分别 = 0.152、0.114 和 0.118）。基于甲基化生物标志物的面板可预测 BE 肿瘤进展，在提高内窥镜检查效率和肿瘤早期检测方面具有潜在的临床价值。
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.