What is Endometriosis? Deep Phenotyping to Advance Diagnosis and Treatment

项目摘要：子宫内膜异位症的女性可能会经历虚弱的盆腔疼痛和不孕症， 生活质量，并承担重大的医疗保健费用。子宫内膜异位症需要手术诊断， 平均延迟7年才能得到诊断。一旦一个女人被诊断出来， 最佳治疗方案和短期和长期预后。子宫内膜异位症是一种异质性疾病， 不仅在疾病表现上，而且在症状表现上。理解和量化这些 异质性是发现非侵入性诊断工具和推进个性化、精确性 治疗方案-本文所述的一个科学空白。我们的建议是鉴别子宫内膜异位症- 特异性炎性、激素和miRNA（转录组）血浆标记物和炎性和 异位子宫内膜（子宫内膜病变）的转录组学谱。我们将量化 这些血浆和组织标记物跨越：（1）子宫内膜异位症诊断时的症状表现，包括疼痛 致敏，（2）手术可视化子宫内膜异位症亚型，和（3）参与者的特征，包括 生殖和妇科病史以及合并症。通过与全球领先的 子宫内膜异位症研究中心（密歇根州立大学，哈佛，牛津大学，Eunice Kennedy Shriver NICHD）和多学科 分子和生理学合作伙伴，我们将解决的假设，1）炎症的组合， 激素和转录血浆标记物可用于区分患有和不患有乳腺癌的妇女。 子宫内膜异位症;和2）激素，炎症和转录血浆和异位的差异 通过评估疾病和症状的异质性， 介绍和参与者的特点。我们进一步假设，这种异质性将告知 治疗反应和预后。我们的综合数据和样本是通过标准操作收集的。 程序，由我们的世界子宫内膜异位症研究基金会子宫内膜异位症表型组和 生物库协调项目（WERF-EPHect）。他们总共有近2000名妇女， 子宫内膜异位症和良好注释的表型数据和血液样本。在子宫内膜异位症患者中， 我们有超过300个已经做好注解的异位子宫内膜样本。 相关性：发现子宫内膜异位症的信息亚型和导致子宫内膜异位症的疾病分类 子宫内膜异位症的精确无创诊断工具和个性化子宫内膜异位症的应用 治疗方案仍然难以捉摸。这导致了诊断的严重延误， 子宫内膜异位症的治疗方法利用我们的多学科团队的专业知识 在生物标志物，子宫内膜异位症异质性和流行病学，提供了前所未有的机会， 推进非侵入性诊断的发现，并推进个性化，精确治疗 发展

Project Summary: Women with endometriosis may experience debilitating pelvic pain and infertility, reduced quality of life and incur significant health care costs. Endometriosis requires a surgical diagnosis, which results in an average delay of seven years to obtain a diagnosis. Once a woman is diagnosed, there is scant data on optimal treatment options and short- and long-term prognosis. Endometriosis is a heterogeneous disease not only in disease presentation but also in symptom presentation. Understanding and quantifying this heterogeneity is a crucial step to discover non-invasive diagnostic tools and to advance personalized, precision treatment options - a scientific gap addressed herein. Our proposal addresses identifying endometriosis- specific inflammatory, hormonal and miRNA (transcriptomic) plasma markers and inflammatory and transcriptomic profiles of the ectopic endometrium (endometrial lesions). We will quantify the heterogeneity in these plasma and tissue markers across: (1) symptom presentation at endometriosis diagnosis including pain sensitization, (2) surgically visualized endometriosis subtypes, and (3) participant characteristics including reproductive and gynecologic history and co-morbidities. Through the collaboration of global leading endometriosis research centers (MSU, Harvard, Oxford, Eunice Kennedy Shriver NICHD), and multidisciplinary molecular and physiology partners, we will address the hypotheses that 1) the combination of inflammatory, hormonal, and transcriptional plasma markers can be used to differentiate women with and without endometriosis; and 2) differences in the hormonal, inflammatory and transcriptional plasma and ectopic endometrial markers can be further refined by assessing the heterogeneity in disease and symptom presentation and participant characteristics. We further hypothesize that this heterogeneity will inform treatment response and prognosis. Our combined data and samples were collected by standard operating procedures, established by our World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (WERF-EPHect). Together they total nearly 2000 women with and without endometriosis and with well-annotated phenotypic data and blood samples. Among women with endometriosis, we have more than 300 existing well-annotated ectopic endometrial samples. Relevance: The discovery of informative subtypes of endometriosis and classifications of disease that lead to precise non-invasive diagnostic tools for endometriosis and the application of personalized endometriosis treatment options have remained elusive. This has resulted in significant delays in diagnosis and potentially financial and personal costs for women with endometriosis. Leveraging our multidisciplinary team with expertise in biomarkers, endometriosis heterogeneity, and epidemiology, provides an unprecedented opportunity to advance the discovery of a non-invasive diagnostic and to advance personalized, precision treatment development.