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整合全基因组表达和启动子 DNA 甲基化谱分析鉴定出一个潜在的新型卵巢癌表观遗传生物标志物面板。

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

机构信息

Cancer Research Program, The Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, New South Wales 2010, Australia.

出版信息

Cancer Lett. 2012 May 1;318(1):76-85. doi: 10.1016/j.canlet.2011.12.003. Epub 2011 Dec 9.

DOI:10.1016/j.canlet.2011.12.003
PMID:22155104
Abstract

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.

摘要

为了鉴定用于卵巢癌诊断的基于表观遗传学的生物标志物,我们在 A2780 和 CaOV3 卵巢癌细胞系中进行了 MeDIP-Chip 实验。通过 Sequenom 质谱甲基化分析进行验证,证实了一组六个基因启动子(ARMCX1、ICAM4、LOC134466、PEG3、PYCARD 和 SGNE1),其甲基化程度可区分 27 例浆液性卵巢癌临床样本与 12 例正常卵巢表面上皮细胞(OSE)(ROC 为 0.98)。值得注意的是,在潜在的长基因间非编码 RNA(lincRNA)基因(LOC134466)转录起始位点的 CpG 位点在 81%的浆液性 EOC 中被高度甲基化,可区分肿瘤与 OSE(p<0.05)。我们提出,该潜在的生物标志物组合有望成为高级别(II 型)浆液性卵巢癌的诊断测试。

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