Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1745 W. Harrison Street, Ste. 309, Chicago, IL 60612, USA.
Gynecol Oncol. 2011 Jan;120(1):113-20. doi: 10.1016/j.ygyno.2010.09.019. Epub 2010 Nov 6.
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.
上皮性卵巢癌（OvCa）早期很少被发现，而且也很难确定附件包块是良性还是恶性。之前，我们注意到无疾病女性的游离血浆 DNA（cfpDNA）的甲基化模式存在差异，而这些差异与 OvCa 患者不同。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和恶性肿瘤。
使用基于微阵列的检测方法（MethDet 56）在三个队列（每个队列 30 个样本）中确定 cfpDNA 的甲基化模式。使用主成分分析、监督聚类、线性判别分析和 25 轮 5 倍交叉验证来确定信息基因，并评估区分 OvCa 与健康对照（HC）、良性卵巢疾病（主要是浆液性囊腺瘤，BOD）与 HC 以及 OvCa 与 BOD 样本的敏感性和特异性。
三个启动子（RASSF1A、CALCA 和 EP300）的差异甲基化可区分 OvCa 与 HC，敏感性为 90.0%，特异性为 86.7%。三个不同的启动子（BRCA1、CALCA 和 CDKN1C）对区分 BOD 与 HC 具有信息性，敏感性为 90.0%，特异性为 76.7%。最后，两个启动子（RASSF1A 和 PGR-PROX）对区分 OvCa 与 BOD 具有信息性，敏感性为 80.0%，特异性为 73.3%。
这一初步数据表明，cfpDNA 中启动子的差异甲基化可能是区分某些良性和恶性卵巢肿瘤的有用生物标志物。
