Progression-Free Survival in Ovarian Cancer Is Reflected in Epigenetic DNA Methylation Profiles
Progression-Free Survival in Ovarian Cancer Is Reflected in Epigenetic DNA Methylation Profiles
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DOI：
10.1159/000327746
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发表时间：
2011-01-01
期刊：
影响因子：
3.5
通讯作者：
Wagner, Wolfgang
中科院分区：
文献类型：
--
作者：
Bauerschlag, Dirk O.;Ammerpohl, Ole;Wagner, Wolfgang
目的：卵巢癌患者多在辅助化疗后6个月内复发，预后有限。表观遗传修饰已被证明在肿瘤的发展和形成中发挥重要作用。因此，DNA甲基化模式的全球分析可能揭示与治疗后无进展间期(PFI)相关的特定CpG位点。方法：对20例晚期卵巢癌组织学亚型以浆液性乳头状癌为主的标本进行DNA甲基化分析。利用Illumina Human Megylation27微珠芯片技术对114,000个基因中的27,578个CpG位点进行了同时分析。结果：不同胞嘧啶的差异DNA甲基化与PFI相关。然而，这只在根据PFI分类时才显着，截止时间为128个月。较长的生存期与特定CpG位点(如GREB1、TGIF和Tob1)的低甲基化和其他基因(如TMCO5、PTPRN和GUCY2C)的高甲基化有关。基因本体论分析表明，差异甲基化基因在端粒组织、中胚层发育和免疫调节等类别中显著过度表达。结论：卵巢癌中特定CpG位点的表观遗传修饰与PFI相关。因此，这种分析可能对预后有价值。版权所有(C)2011 S.Karger AG，巴塞尔
Objective: Many patients with ovarian cancer disease relapse within 6 months after adjuvant chemotherapy, with a limited prognosis. Epigenetic modifications have been shown to play an important role in tumor development and formation. Therefore, global analysis of DNA methylation patterns might reveal specific CpG sites that correlate with progression-free interval (PFI) after therapy. Methods: Twenty samples of advanced ovarian cancer with a predominantly serous papillary histological subtype were subjected to DNA methylation profiling. Illumina HumanMethylation27 BeadChip technology was used for simultaneous analysis of 27,578 CpG sites in 1 14,000 genes. Results: Differential DNA methylation of various cytosines correlated with PFI. However, this becomes only significant by classification according to PFI with a cutoff of 1 28 months. Longer survival was associated with hypomethylation at specific CpG sites (e. g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e. g. TMCO5, PTPRN and GUCY2C). Gene ontology analysis revealed that differentially methylated genes were significantly overrepresented in the categories telomere organization, mesoderm development and immune regulation. Conclusion: Epigenetic modifications at specific CpG sites correlate with PFI in ovarian cancer. Therefore, such analysis might be of prognostic value. Copyright (C) 2011 S. Karger AG, Basel