Analysis of DNA Methylation in Bowel Lavage Fluid for Detection of Colorectal Cancer
Analysis of DNA Methylation in Bowel Lavage Fluid for Detection of Colorectal Cancer
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DOI：
10.1158/1940-6207.capr-14-0162
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发表时间：
2014-10-01
影响因子：
3.3
通讯作者：
Suzuki, Hiromu
中科院分区：
文献类型：
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作者：
Harada, Taku;Yamamoto, Eiichiro;Suzuki, Hiromu
异常的 DNA 甲基化有可能作为结直肠肿瘤的生物标志物。在这项研究中，我们评估了利用肠灌洗液 (BLF) 中检测到的 DNA 甲基化进行结直肠癌筛查的可行性。共收集了 508 份 BLF 标本，来自接受结肠镜检查的结直肠癌患者 (n = 56)、晚期腺瘤 (n = 53)、小息肉 (n = 209) 和健康个体 (n = 190)。然后在 MethyLight 中分析 15 个基因（miR-1-1、miR-9-1、miR-9-3、miR-34b/c、miR-124-1、miR-124-2、miR-124-3、miR-137、SFRP1、SFRP2、APC、DKK2、WIF1、LOC386758 和 ZNF582）的甲基化分析，然后分析受试者工作特征（ROC）曲线以评估 BLF 甲基化的诊断性能。通过分析训练集中的 BLF 样本 (n = 345)，我们选择了对结直肠癌检测表现出最高敏感性的三个基因 (miR-124-3, 71.8%; LOC386758, 79.5%; 和 SFRP1, 74.4%)。基于这三个基因甲基化（M-score）的评分系统实现了 82% 的敏感性和 79% 的特异性，ROC 曲线下面积 (AUC) 为 0.834。然后，该系统的强大性能在独立测试集中得到了验证（n = 153；AUC = 0.808）。 M评分与结直肠癌的临床病理特征之间没有发现显着相关性。我们的结果表明，BLF 样本中的 DNA 甲基化可能是检测结直肠癌的有用生物标志物。 (C) 2014 年 AACR。
Aberrant DNA methylation could potentially serve as a biomarker for colorectal neoplasms. In this study, we assessed the feasibility of using DNA methylation detected in bowel lavage fluid (BLF) for colorectal cancer screening. A total of 508 BLF specimens were collected from patients with colorectal cancer (n = 56), advanced adenoma (n = 53), minor polyp (n = 209), and healthy individuals (n = 190) undergoing colonoscopy. Methylation of 15 genes (miR-1-1, miR-9-1, miR-9-3, miR-34b/c, miR-124-1, miR-124-2, miR-124-3, miR-137, SFRP1, SFRP2, APC, DKK2, WIF1, LOC386758, and ZNF582) was then analyzed in MethyLight assays, after which receiver operating characteristic (ROC) curves were analyzed to assess the diagnostic performance of BLF methylation. Through analyzing BLF specimens in a training set (n = 345), we selected the three genes showing the greatest sensitivity for colorectal cancer detection (miR-124-3, 71.8%; LOC386758, 79.5%; and SFRP1, 74.4%). A scoring system based on the methylation of those three genes (M-score) achieved 82% sensitivity and 79% specificity, and the area under the ROC curve (AUC) was 0.834. The strong performance of this system was then validated in an independent test set (n = 153; AUC = 0.808). No significant correlation was found between M-score and the clinicopathologic features of the colorectal cancers. Our results demonstrate that DNA methylation in BLF specimens may be a useful biomarker for the detection of colorectal cancer. (C) 2014 AACR.