Genome-scale screen for DNA methylation-based detection markers for ovarian cancer.
Genome-scale screen for DNA methylation-based detection markers for ovarian cancer.
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DOI：
10.1371/journal.pone.0028141
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Laird PW
中科院分区：
文献类型：
--
作者：
Campan M;Moffitt M;Houshdaran S;Shen H;Widschwendter M;Daxenbichler G;Long T;Marth C;Laird-Offringa IA;Press MF;Dubeau L;Siegmund KD;Wu AH;Groshen S;Chandavarkar U;Roman LD;Berchuck A;Pearce CL;Laird PW
鉴定用于检测卵巢癌的敏感生物标志物对于早期检测和/或监测疾病复发具有高度临床相关性。我们开发了一种系统的多步骤生物标志物发现和验证策略，以确定用于基于血液检测卵巢癌的候选DNA甲基化标志物。我们使用Illumina Infinium平台分析了41例卵巢肿瘤中27，578个CpG位点的DNA甲基化状态。我们采用了一种标记物选择策略，通过要求肿瘤间甲基化的一致性来强调灵敏度，同时通过排除对照白细胞或血清DNA中具有甲基化的标记物来实现特异性。我们的验证策略包括检测所鉴定的标志物在连续收集的卵巢癌患者血清样品中监测疾病负荷的能力，所述卵巢癌患者经历了手术肿瘤切除术，与CA-125水平相比。我们鉴定了一种标记物，IFFO 1启动子甲基化（IFFO 1-M），它在卵巢肿瘤中频繁甲基化，而在正常对照的血液中很少检测到。当在127个连续收集的卵巢癌患者的血清中进行测试时，IFFO 1-M在16个患者中的6个中显示出与血清CA-125测量值显著相关的切除后动力学。我们实施了一个有效的标记物筛选和验证策略，导致IFFO 1-M作为一个基于血液的候选标记物，用于卵巢癌的敏感检测。IFFO 1-M的血清水平显示与疾病负荷的反映一致的切除后动力学。我们预计，IFFO 1-M和其他候选标记物出现在这个标记物开发管道可能提供疾病检测能力，补充现有的生物标志物。
The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer. We used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels. We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients. We implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers.
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DOI：
10.1093/jnci/djp438
发表时间：
2010-01-06
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Anderson GL;McIntosh M;Wu L;Barnett M;Goodman G;Thorpe JD;Bergan L;Thornquist MD;Scholler N;Kim N;O'Briant K;Drescher C;Urban N
通讯作者：
Urban N
影响因子：
4.7
作者：
Moore, Richard G.;Brown, Amy K.;Bast, Robert C., Jr.
通讯作者：
Bast, Robert C., Jr.
关键评估用于分类或预测的生物标志物的准确性：研究设计标准。
影响因子：
10.3
作者：
Pepe, Margaret S.;Feng, Ziding;Janes, Holly;Bossuyt, Patrick M.;Potter, John D.
通讯作者：
Potter, John D.
影响因子：
14.9
作者：
Eads, Cindy A.;Danenberg, Kathleen D.;Laird, Peter W.
通讯作者：
Laird, Peter W.
影响因子：
3.5
作者：
Byun, Hyang-Min;Siegmund, Kimberly D.;Yang, Allen S.
通讯作者：
Yang, Allen S.