Global methylation profile in endometrium of endometriosis patients

描述(申请人提供)：子宫内膜异位症是一种常见的妇科疾病，病因不明，可导致剧烈疼痛和不孕不育。目前，子宫内膜异位症的非侵入性诊断缺乏，因此诊断的金标准依赖于腹腔镜术。由于与腹腔镜术相关的高成本和额外风险，以及缺乏明确的诊断临床症状，从症状出现到诊断平均延迟10年。综上所述，对子宫内膜异位症的非侵入性诊断有巨大的需求，以减少如此长的治疗时间。有越来越多的证据表明，患者子宫内膜中特定基因的DNA甲基化改变和DNA甲基转移酶的表达增加。然而，到目前为止，还缺乏对子宫内膜组织DNA甲基化状态的全球分析。我们假设患者将具有与对照组不同的全球DNA甲基化特征。明确这一特征将进一步加深对子宫内膜异位症病理生理学的理解，并将为开发新的诊断和治疗方法提供新的靶点。该项目的总体目标是确定子宫内膜异位症患者子宫内膜的全球甲基化状态，并利用这一知识为新的诊断选择标记物。虽然这个项目的长期目标是开发一种非侵入性的子宫内膜异位症诊断测试，但这一应用程序的具体目标是确定潜在的诊断目标。具体地说，患者子宫内膜组织的全球DNA甲基化模式将与无疾病对照组的DNA甲基化模式进行比较。回归模型将被用来确定那些受潜在混杂因素影响最小的标记。预计这项拟议研究的完成将为开发一种新的、非侵入性的子宫内膜异位症诊断方法提供坚实的基础，并对子宫内膜异位症患者产生持续而强大的影响。所提出的方法学方法有助于将识别的目标快速转换为最小或完全非侵入性的快速诊断。这些研究的结果将被用来显著缩短诊断的潜伏期，从而减少患者遭受疼痛和/或不孕的时间。 公共卫生相关性：目前不可能在不做手术的情况下诊断子宫内膜异位症。该项目将是第一个探索到目前为止基本上被忽视的重要组成部分的项目。预计拟议研究的结果将被用来显著减少诊断时间，从而减少患者遭受这种疾病的时间。此外，开发一种非侵入性或微创性的子宫内膜异位症诊断测试将防止不必要的腹腔镜检查。因此，通过避免不必要的昂贵的外科手术并提供早期诊断，这项工作将进一步降低与治疗子宫内膜异位症相关的成本。

DESCRIPTION (provided by applicant): Endometriosis is a common gynecological disease with unknown etiology that can cause severe pain and infertility. Presently a non-invasive diagnostic test for endometriosis is lacking and thus the gold standard for diagnosis is dependent on laparoscopy. Due to the high cost and additional risk associated with laparoscopy and the absence of definitive diagnostic clinical symptoms, there is a 10-year average delay from onset of symptoms to diagnosis. Taken together, there is a huge need for a noninvasive diagnostic for endometriosis to decrease this long time to treatment. There is growing evidence of altered DNA methylation of specific genes and increased expression of DNA methyltransferases in patient endometrium. However, to date a global analysis of the DNA methylation status of endometrial tissue is lacking. We hypothesize that patients will have a global DNA methylation profile distinct from controls. Defining this profile will further the understanding of the pathophysiology of endometriosis and in so doing, will provide new targets to develop novel diagnostics and therapeutics. The overall goal of this project is to define the global methylation status in the endometrium of women with endometriosis and to use this knowledge to select markers for a novel diagnostic. While the long-term goal of this project is to develop a non-invasive diagnostic test for endometriosis, the specific goal of this application is to identify potential diagnostic targets. Specifically, global DNA methylation patterns of endometrial tissue from patients will be compared to those of disease free controls. A regression model will be used to identify those markers least affected by potential confounding factors. It is strongly anticipated that completion of the proposed study will provide a solid foundation for development of a novel, noninvasive diagnostic for endometriosis and have a sustained and powerful impact on patients with endometriosis. The proposed methodological approach lends itself to rapid translation of identified targets to a minimally or completely non-invasive, rapid diagnostic. The results of these studies will be used to significantly decrease the latency of diagnosis and thereby decrease the amount of time that patients suffer from pain and/or infertility. PUBLIC HEALTH RELEVANCE: It is currently not possible to diagnose endometriosis without surgery. This project will be the first to explore an important and thus far largely overlooked component. It is anticipated that the results of the proposed studies will be used to significantly decrease the time to diagnosis and thereby decrease the amount of time that patients suffer from this disease. Furthermore, the development of a non- or minimally-invasive diagnostic test for endometriosis will prevent unnecessary laparoscopies. Thus, by preventing unnecessary, expensive surgical procedures and providing an earlier diagnosis, this work will further reduce the cost associated with treating endometriosis.