Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors.
Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors.
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DOI：
10.1016/j.ygyno.2010.09.019
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发表时间：
2011-01
影响因子：
4.7
通讯作者：
Levenson V
中科院分区：
文献类型：
--
作者：
Liggett TE;Melnikov A;Yi Q;Replogle C;Hu W;Rotmensch J;Kamat A;Sood AK;Levenson V
卵巢上皮癌(OvCa)很少早期发现，也很难确定附件肿块是良性的还是恶性的。此前，我们注意到与卵巢癌患者相比，没有疾病的女性患者的无细胞血浆DNA(CfpDNA)甲基化模式有所不同。在这项工作中，我们研究了cfpDNA的甲基化模式是否可以区分良性肿瘤和恶性肿瘤。使用基于微阵列的分析方法(MethDet 56)在三个队列(每个队列30个样本)中确定了cfpDNA的甲基化模式。应用主成分分析、监督聚类、线性判别分析和25轮5轮交叉验证来确定信息性基因，并评估卵巢良性疾病(主要是浆液性囊腺瘤)与健康对照(HC)、卵巢良性疾病(主要是浆液性囊腺瘤)与HC以及OvCA与BOD样本之间的鉴别的敏感性和特异性。3个启动子(RASSF1A、Calca和EP300)的甲基化水平在OvCa和HC之间的差异有90.0%的敏感性和86.7%的特异性。3种不同启动子(BRCA1、CALCA和CDKN1C)对鉴别BOD和HC的敏感性为90.0%，特异性为76.7%。两个启动子(RASSF1A和PGR-prox)对鉴别OvCa和BOD的敏感性为80.0%，特异性为73.3%。这一原理验证数据表明，cfpDNA启动子的差异甲基化可能是区分某些卵巢良性肿瘤和恶性肿瘤的有用生物标志物。
Epithelial ovarian carcinoma (OvCa) is rarely detected early, and it is also difficult to determine whether an adnexal mass is benign or malignant. Previously, we noted differences in methylation patterns of cell-free plasma DNA (cfpDNA) in women without disease compared to patients with OvCa. In this work we investigated whether methylation patterns of cfpDNA can differentiate between benign and malignant tumors. Methylation patterns in cfpDNA were determined in three cohorts (30 samples each) using a microarray-based assay (MethDet 56). Principal component analysis, supervised clustering, linear discrimination analysis, and 25 rounds of 5-fold cross validation were used to determine informative genes and assess the sensitivity and specificity of differentiating between OvCa vs. healthy control (HC), benign ovarian disease (mostly serous cystadenoma, BOD) vs. HC, and OvCa vs. BOD samples. Differential methylation of three promoters (RASSF1A, CALCA, and EP300) differentiated between OvCa vs. HC with a sensitivity of 90.0% and a specificity of 86.7%. Three different promoters (BRCA1, CALCA, and CDKN1C) were informative for differentiating between BOD vs. HC, with a sensitivity of 90.0% and a specificity of 76.7%. Finally, two promoters (RASSF1A and PGR-PROX) were informative for differentiating between OvCa vs. BOD, with a sensitivity of 80.0% and a specificity of 73.3%. This proof-of-principle data show that differential methylation of promoters in cfpDNA may be a useful biomarker to differentiate between certain benign and malignant ovarian tumors.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
6.2
作者：
Liggett, Thomas;Melnikov, Anatoliy;Levenson, Victor
通讯作者：
Levenson, Victor
影响因子：
11.5
作者：
Gifford, G;Paul, J;Brown, R
通讯作者：
Brown, R
DOI：
10.1067/s0002-9378(03)00579-9
发表时间：
2003-10-01
影响因子：
9.8
作者：
Barnholtz-Sloan, JS;Schwartz, AG;Munkarah, AR
通讯作者：
Munkarah, AR
DOI：
10.1097/gme.0b013e3181aa1c93
发表时间：
2009-11-01
影响因子：
2.7
作者：
Bell, Robin J.;Healy, David L.;Walker, Frances
通讯作者：
Walker, Frances