An epigenetic signature in peripheral blood predicts active ovarian cancer.
An epigenetic signature in peripheral blood predicts active ovarian cancer.
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DOI：
10.1371/journal.pone.0008274
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发表时间：
2009-12-18
期刊：
影响因子：
3.7
通讯作者：
Widschwendter M
中科院分区：
文献类型：
--
作者：
Teschendorff AE;Menon U;Gentry-Maharaj A;Ramus SJ;Gayther SA;Apostolidou S;Jones A;Lechner M;Beck S;Jacobs IJ;Widschwendter M
最近的研究表明，外周血中的DNA甲基化（DNA m）标记物可能有望作为上皮癌的诊断或早期检测/风险标记物。然而，迄今为止，没有研究评估了诊断和预测潜力，这些标志物在一个大的病例对照队列和全基因组的基础上。通过对一个大型卵巢癌病例对照组进行全基因组DNA图谱分析，我们在此证明活动性卵巢癌对外周血DNA图谱有显著影响。具体来说，通过测量来自148名健康个体和113名年龄匹配的治疗前卵巢癌病例的血细胞中超过27，000个CpG的甲基化水平，我们得出了一个DNAm特征，可以预测盲法测试集中活动性卵巢癌的存在，AUC为0.8（95%CI（0.74-0.87））。我们在另一组122例治疗后病例中进一步验证了我们的发现（AUC = 0.76（0.72-0.81））。 此外，我们还提供了大量卵巢癌候选风险或早期检测标志物的证据。此外，通过将甲基化模式与主要血细胞类型的基因表达数据进行比较，我们在这里证明了年龄和癌症引起外周血组成的常见变化，随着年龄的增长，骨髓偏斜进一步加剧卵巢癌的存在。最后，我们发现，大多数癌症和年龄相关的甲基化变异是在位于CpG岛以外的CpG。我们的研究结果强调了外周血DNAm谱作为上皮癌检测或风险预测工具的潜力，并保证进一步深入和更高的CpG覆盖率研究，以进一步阐明这一作用。
Recent studies have shown that DNA methylation (DNAm) markers in peripheral blood may hold promise as diagnostic or early detection/risk markers for epithelial cancers. However, to date no study has evaluated the diagnostic and predictive potential of such markers in a large case control cohort and on a genome-wide basis. By performing genome-wide DNAm profiling of a large ovarian cancer case control cohort, we here demonstrate that active ovarian cancer has a significant impact on the DNAm pattern in peripheral blood. Specifically, by measuring the methylation levels of over 27,000 CpGs in blood cells from 148 healthy individuals and 113 age-matched pre-treatment ovarian cancer cases, we derive a DNAm signature that can predict the presence of active ovarian cancer in blind test sets with an AUC of 0.8 (95% CI (0.74–0.87)). We further validate our findings in another independent set of 122 post-treatment cases (AUC = 0.76 (0.72–0.81)). In addition, we provide evidence for a significant number of candidate risk or early detection markers for ovarian cancer. Furthermore, by comparing the pattern of methylation with gene expression data from major blood cell types, we here demonstrate that age and cancer elicit common changes in the composition of peripheral blood, with a myeloid skewing that increases with age and which is further aggravated in the presence of ovarian cancer. Finally, we show that most cancer and age associated methylation variability is found at CpGs located outside of CpG islands. Our results underscore the potential of DNAm profiling in peripheral blood as a tool for detection or risk-prediction of epithelial cancers, and warrants further in-depth and higher CpG coverage studies to further elucidate this role.
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影响因子：
11.2
作者：
Christensen, Brock C.;Houseman, E. A.;Kelsey, Karl T.
通讯作者：
Kelsey, Karl T.
DOI：
10.1111/j.1749-6632.2003.tb03247.x
发表时间：
2003-01-01
期刊：
HEMATOPOIETIC STEM CELLS 2002: GENETICS AND FUNCTION
影响因子：
--
作者：
Kim, M;Moon, HM;Spangrude, GJ
通讯作者：
Spangrude, GJ
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1196/annals.1395.005
发表时间：
2007-01-01
期刊：
BIOGERONTOLOGY: MECHANISMS AND INTERVENTIONS
影响因子：
--
作者：
Fraga, Mario F.;Agrelo, Ruben;Esteller, Manel
通讯作者：
Esteller, Manel
影响因子：
56.9
作者：
Cui, HM;Cruz-Correa, M;Feinberg, AP
通讯作者：
Feinberg, AP