Global methylation profile in endometrium of endometriosis patients

子宫内膜异位症患者子宫内膜的整体甲基化谱

• 批准号: 8331373
• 负责人: SUSAN C NAGEL
• 金额: $ 22.73万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-09 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8331373
• 关键词: Affect; Age; Animal Model; Biological Assay; Biopsy; Clinical; Confounding Factors (Epidemiology); Cost of Illness; CpG Islands; DNA; DNA Methylation; DNA Methyltransferase; DNA Modification Methylases; Development; Diagnosis; Diagnostic; Diagnostic tests; Discrimination; Disease; Early Diagnosis; Endometrial; Endometrium; Environment; Etiology; Fertility; Foundations; Functional disorder; Future; Gene Expression; Gene Expression Profile; Genes; Goals; Gold; Greater sac of peritoneum; Growth; Immune system; Implant; Infertility; Knowledge; Laparoscopy; Lead; Measurement; Measures; Methylation; Microarray Analysis; Modeling; Operative Surgical Procedures; Pain; Patients; Pattern; Peritoneal; Quality of life; Recovery; Retrograde Menstruation; Risk; Smoking Status; Solid; Staging; Symptoms; Technology; Testing; Time; Tissues; Translating; Translations; Uterus; Validation; Woman; Women' s Health; Work; base; clinically significant; cost; diagnosis standard; endometriosis; improved; interest; minimally invasive; novel; novel diagnostics; novel therapeutics; parity; prevent; promoter; validation studies

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.

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，可引起剧烈疼痛和不孕。目前，子宫内膜异位症的非侵入性诊断测试缺乏，因此诊断的金标准依赖于腹腔镜检查。由于腹腔镜检查的高费用和额外的风险，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，子宫内膜异位症迫切需要一种无创诊断方法来缩短治疗时间。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，迄今为止，缺乏对子宫内膜组织DNA甲基化状态的全局分析。我们假设患者将具有与对照组不同的全局DNA甲基化谱。定义这一概况将进一步了解子宫内膜异位症的病理生理学，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女性子宫内膜的整体甲基化状态，并利用这一知识选择新的诊断标记。虽然该项目的长期目标是开发子宫内膜异位症的非侵入性诊断测试，但该应用程序的具体目标是确定潜在的诊断目标。具体而言，将患者子宫内膜组织的整体DNA甲基化模式与无疾病对照进行比较。回归模型将用于识别那些受潜在混杂因素影响最小的标记。我们强烈期望这项研究的完成将为开发一种新的、无创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有力的影响。所提出的方法方法使其能够将已确定的目标快速翻译为最小或完全无创的快速诊断。这些研究的结果将用于显著减少诊断的潜伏期，从而减少患者遭受疼痛和/或不孕症的时间。