DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps.
DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps.
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DOI：
10.1002/ijc.26484
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发表时间：
2012-09-01
影响因子：
6.4
通讯作者：
Levenson, Victor
中科院分区：
文献类型：
--
作者：
Cassinotti, Elisa;Melson, Joshua;Liggett, Thomas;Melnikov, Anatoliy;Yi, Qilong;Replogle, Charles;Mobarhan, Sohrab;Boni, Luigi;Segato, Sergio;Levenson, Victor
结直肠癌(CRC)筛查率目前处于次优水平。基于血液的筛查可以提高结直肠癌和腺瘤性结直肠息肉的早期发现率。在这项研究中，我们评估了基于血浆的早期结直肠癌和腺瘤性息肉检测的可行性，方法是对56个与癌变有关的基因进行阵列介导的甲基化分析。将I、II期结直肠癌患者(N=30)和腺瘤性息肉患者(N=30)的56个基因甲基化与接受结肠镜检查的患者进行比较，发现这些患者既没有腺瘤改变，也没有结直肠癌。开发了腺瘤性息肉和结直肠癌的复合生物标志物，并通过五次交叉验证评估了它们的敏感性和特异性。选择6个启动子(CyCD2、HIC1、PAX 5、RASSF1A、RB1和SRBC)作为生物标志物，区分CRC患者和对照组，敏感性和特异性分别为84%和68%。选择3个启动子(HIC1、MDG1和RASSF1A)作为生物标志物，区分腺瘤性息肉患者和对照组，其敏感性和特异性分别为55%和65%。血浆DNA甲基化分析可以非常准确地检测早期结直肠癌，并显示出作为一种方法学开发结直肠癌筛查生物标志物的前景。
Colorectal cancer (CRC) screening rates are currently suboptimal. Blood-based screening could improve rates of earlier detection for CRC and adenomatous colorectal polyps. In this study, we evaluated the feasibility of plasma-based detection of early CRC and adenomatous polyps using array-mediated analysis methylation profiling of 56 genes implicated in carcinogenesis. Methylation of 56 genes in patients with stage I and II CRC (N=30) and those with adenomatous polyps (N=30) were compared to individuals who underwent colonoscopy and were found to have neither adenomatous changes nor CRC. Composite biomarkers were developed for adenomatous polyps and CRC, and their sensitivity and specificity was estimated using five-fold cross validation. Six promoters (CYCD2, HIC1, PAX 5, RASSF1A, RB1, and SRBC) were selected for the biomarker, which differentiated CRC patients and controls with 84% sensitivity and 68% specificity. Three promoters (HIC1, MDG1, and RASSF1A) were selected for the biomarker, which differentiated patients with adenomatous polyps and controls with sensitivity of 55% and specificity of 65%. Methylation profiling of plasma DNA can detect early CRC with significant accuracy and shows promise as a methodology to develop biomarkers for CRC screening.
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影响因子：
6.2
作者：
Liggett, Thomas;Melnikov, Anatoliy;Levenson, Victor
通讯作者：
Levenson, Victor
影响因子：
24.5
作者：
Citarda, F;Tomaselli, G;Crespi, M
通讯作者：
Crespi, M
影响因子：
6.4
作者：
Liggett, Thomas E.;Melnikov, Anatoliy A.;Marks, Jeffrey R.;Levenson, Victor V.
通讯作者：
Levenson, Victor V.
影响因子：
7.5
作者：
Dong, SM;Lee, EJ;Kim, KM
通讯作者：
Kim, KM
影响因子：
9.3
作者：
Lofton-Day, Catherine;Model, Fabian;Sledziewski, Andrew
通讯作者：
Sledziewski, Andrew