Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers

Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers
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DOI:
10.1016/j.canlet.2011.12.003
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发表时间:
2012-05-01
期刊:
影响因子:
9.7
通讯作者:
Clark, Susan J.
Clark, Susan J.
中科院分区:
医学1区
文献类型:
--
作者:
Gloss, Brian S.;Patterson, Kate I.;Clark, Susan J.

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为了鉴定用于诊断卵巢癌的基于表观遗传学的生物标志物,我们在A2780和CaOV 3卵巢癌细胞系中进行MeDIP-芯片。通过Sequenom massARRAY甲基化分析的验证证实了一组六个基因启动子(ARMCX 1、ICAM 4、L0 C134466、PEG 3、PYCARD和SGNE 1),其中超甲基化区分了27个浆液性卵巢癌临床样品与12个正常卵巢表面上皮细胞(OSE)(ROC为0.98)。值得注意的是,跨越潜在的长基因间非编码RNA(lincRNA)基因(L0 C134466)的转录起始位点的CpG位点在81%的浆液性EOC中显示出高甲基化,并且可以将肿瘤与OSE区分开(p < 0.05)。我们认为,这种潜在的生物标志物面板作为高级别(II型)浆液性卵巢癌的诊断测试有很大的希望。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
To identify epigenetic-based biomarkers for diagnosis of ovarian cancer we performed MeDIP-Chip in A2780 and CaOV3 ovarian cancer cell lines. Validation by Sequenom massARRAY methylation analysis confirmed a panel of six gene promoters (ARMCX1, ICAM4, LOC134466, PEG3, PYCARD & SGNE1) where hypermethylation discriminated 27 serous ovarian cancer clinical samples versus 12 normal ovarian surface epithelial cells (OSE) (ROC of 0.98). Notably, CpG sites across the transcription start site of a potential long-intergenic non-coding RNA (lincRNA) gene (LOC134466), was shown to be hypermethylated in 81% of serous EOC and could differentiate tumours from OSE (p < 0.05). We propose that this potential biomarker panel holds great promise as a diagnostic test for high-grade (Type II) serous ovarian cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved.