NotI microarrays: novel epigenetic markers for early detection and prognosis of high grade serous ovarian cancer.

NotI microarrays: novel epigenetic markers for early detection and prognosis of high grade serous ovarian cancer.
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Noti微阵列:高级浆液卵巢癌的早期检测和预后的新型表观遗传标记。

DOI:
10.3390/ijms131013352
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发表时间:
2012-10-18
影响因子:
5.6
通讯作者:
Zabarovsky E
Zabarovsky E
中科院分区:
生物学2区
文献类型:
--
作者:
Kashuba V;Dmitriev AA;Krasnov GS;Pavlova T;Ignatjev I;Gordiyuk VV;Gerashchenko AV;Braga EA;Yenamandra SP;Lerman M;Senchenko VN;Zabarovsky E

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应用3号染色体特异性NotI基因芯片(NMA)分析了18例高级别浆液性卵巢癌(HGSOC)和7例良性卵巢肿瘤的180个克隆和188个基因。我们的目的是寻找新的甲基化依赖性生物标志物,用于HGSOC的早期检测和预后。35个NotI标记显示甲基化/缺失频率大于或等于17%。为了检查NMA杂交的结果,对四种基因(LRRC 3B、THRB、ITGA 9和RBSP 3(CTDSPL))的几个样品进行亚硫酸氢盐测序并确认NMA杂交的结果。一组八种生物标志物:NKIRAS 1/RPL 15、THRB、RBPS 3(CTDSPL)、IQSEC 1、NBEAL 2、ZIC 4、LOC 285205和FOXP 1被鉴定为能够检测早期和晚期卵巢癌的最突出的集合。本方法的敏感性为(72 ± 11)%,特异性为(94 ± 5)%。早期阶段是最难发现的病例。为了区分卵巢癌的I + II期和III + IV期,最有前景的生物标志物组将包括L0 C285205、CGGBP 1、EPHB 1和NKIRAS 1/RPL 15。本组诊断的敏感性为(80 ± 13)%,特异性为(88 ± 12)%。使用这种技术,我们计划用新的上皮性卵巢癌样本来验证这个面板,并添加来自其他染色体的标记。
Chromosome 3-specific NotI microarray (NMA) containing 180 clones with 188 genes was used in the study to analyze 18 high grade serous ovarian cancer (HGSOC) samples and 7 benign ovarian tumors. We aimed to find novel methylation-dependent biomarkers for early detection and prognosis of HGSOC. Thirty five NotI markers showed frequency of methylation/deletion more or equal to 17%. To check the results of NMA hybridizations several samples for four genes (LRRC3B, THRB, ITGA9 and RBSP3 (CTDSPL)) were bisulfite sequenced and confirmed the results of NMA hybridization. A set of eight biomarkers: NKIRAS1/RPL15, THRB, RBPS3 (CTDSPL), IQSEC1, NBEAL2, ZIC4, LOC285205 and FOXP1, was identified as the most prominent set capable to detect both early and late stages of ovarian cancer. Sensitivity of this set is equal to (72 ± 11)% and specificity (94 ± 5)%. Early stages represented the most complicated cases for detection. To distinguish between Stages I + II and Stages III + IV of ovarian cancer the most perspective set of biomarkers would include LOC285205, CGGBP1, EPHB1 and NKIRAS1/RPL15. The sensitivity of the set is equal to (80 ± 13)% and the specificity is (88 ± 12)%. Using this technique we plan to validate this panel with new epithelial ovarian cancer samples and add markers from other chromosomes.
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