What is Endometriosis? Deep Phenotyping to Advance Diagnosis and Treatment

什么是子宫内膜异位症？

基本信息

批准号：
10155536
负责人：
Asgerally T. Fazleabas
金额：
$ 94.44万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10155536
关键词：
Address Adhesions Adolescence Adolescent Adult Age Alcohol consumption Anthropometry Appearance Autoimmune Biological Biological Markers Blood Blood specimen Boston Cardiovascular Diseases Caring Case-Control Studies Characteristics Cicatrix Classification Clinic Clinical Collaborations Communities Data Dermatologic Diagnosis Disease Disease Marker Disease Progression Endometrial Endometriomas Endometrium Enrollment Epidemiology Etiology Face Female Foundations General Population Genetic Transcription Geographic Locations Goals Gynecologic Health Care Costs Heterogeneity Hormonal Hospitals Image-Guided Surgery Immunologic Markers Incidence Infertility Inflammatory Infrastructure International Laparoscopy Laparotomy Lead Lesion Life Style Longitudinal cohort Medical Records Mental Health Methods MicroRNAs Molecular Morbidity - disease rate National Institute of Child Health and Human Development Natural History Operative Surgical Procedures Outcome Study Pain Participant Pathway interactions Patients Pattern Pelvic Pain Peritoneal Peritoneal Diseases Phenotype Physiology Plasma Precision therapeutics Premenopause Prevalence Procedures Productivity Prognosis Quality of life Recording of previous events Research Risk Sampling Scientist Staging Symptoms Time Tissue Sample Tissues Urine Woman Women&apos s Health Work advanced disease base biobank cancer diagnosis cancer therapy cigarette smoking clinical research site cohort collaborative approach comorbidity cost disease classification disease phenotype endometriosis experience functional status inflammatory marker information classification multidisciplinary noninvasive diagnosis novel optimal treatments personalized diagnostics phenome phenotypic data reproductive response sample collection therapy development tool transcriptomics treatment response young woman

项目摘要

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.

项目摘要：子宫内膜异位症的女性可能会使骨盆疼痛和不育会衰弱，减少生活质量和巨大的医疗保健费用。子宫内膜异位症需要手术诊断，这会导致平均延迟七年以获得诊断。一旦诊断出女人，就会有很少的数据最佳治疗选择以及短期和长期预后。子宫内膜异位症是一种异质性疾病仅在疾病表现中，但在症状表现中也是如此。理解和量化这一点异质性是发现非侵入性诊断工具并提高个性化精确度的关键步骤治疗方案 - 本文解决的科学差距。我们的建议介绍了识别子宫内膜异位症 - 特定的炎症，激素和miRNA（转录组）等离子体标记以及炎症性和异位子宫内膜（子宫内膜病变）的转录组谱。我们将量化异质性这些血浆和组织标记遍布：（1）子宫内膜异位症诊断时的症状表现包括疼痛致敏性，（2）手术可视化的子宫内膜异位症亚型，（3）参与者特征包括生殖和妇科历史和合并症。通过全球领导的合作子宫内膜异位研究中心（MSU，哈佛，牛津，Eunice Kennedy Shriver Nichd）和多学科分子和生理伙伴，我们将解决以下假设：1）炎症的组合，激素和转录等离子体标记可用于区分有或没有的女性子宫内膜异位症； 2）激素，炎症和转录等离子体和异位的差异可以通过评估疾病和症状的异质性来进一步完善子宫内膜标记演示和参与者特征。我们进一步假设这种异质性将告知治疗反应和预后。我们的组合数据和样品是通过标准操作收集的我们世界子宫内膜异位研究基金会子宫内膜异位症现象和生物库协调项目（WERF-EPHECT）。他们在一起总共有近2000名，没有和没有子宫内膜异位症以及宣布良好的表型数据和血液样本。在子宫内膜异位症的女性中我们有300多个现有良好的异位子宫内膜样品。相关性：发现子宫内膜异位症和疾病分类的信息亚型精确的非侵入性诊断工具用于子宫内膜异位症和个性化子宫内膜异位症的应用治疗方案仍然难以捉摸。这导致诊断和潜在的延迟子宫内膜异位症女性的财务和个人费用。通过专业知识利用我们的多学科团队在生物标志物中，子宫内膜异位异质性和流行病学为前所未有的机会提供了机会推进发现非侵入性诊断并提高个性化的精确治疗发展。