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：
9751909
负责人：
Asgerally T. Fazleabas
金额：
$ 63.67万
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/9751909
关键词：
Address Adhesions Adolescence Adolescent Adult Age Alcohol consumption Anthropometry Appearance Autoimmune Process Biological Biological Markers Blood Blood specimen Boston Cardiovascular Diseases Caring Case-Control Studies Characteristics Cicatrix Classification Clinic Clinical Collaborations Communities Comorbidity 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 Gynecology 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 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 cost disease classification disease phenotype endometriosis experience functional status inflammatory marker information classification multidisciplinary noninvasive diagnosis novel optimal treatments outcome forecast 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：患有子宫内膜异位症的女性可能会经历令人衰弱的盆腔疼痛和不孕症，从而减少生活质量并产生大量的医疗保健费用。子宫内膜异位症需要手术诊断，结果平均延迟七年才能获得诊断。一旦女性被确诊，关于这方面的数据很少最佳治疗方案以及短期和长期预后。子宫内膜异位症是一种异质性疾病，不是不仅在疾病表现上，而且在症状表现上。理解并量化这一点异质性是发现非侵入性诊断工具和推进个性化、精准化的关键一步治疗方案——本文解决的科学差距。我们的提案涉及识别子宫内膜异位症 - 特定炎症、激素和 miRNA（转录组）血浆标记物以及炎症和异位子宫内膜（子宫内膜病变）的转录组学特征。我们将量化异质性这些血浆和组织标志物涵盖：（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，以及 (3) 参与者特征，包括生殖和妇科病史以及合并症。通过全球领先的合作子宫内膜异位症研究中心（密歇根州立大学、哈佛大学、牛津大学、尤尼斯·肯尼迪·施莱弗·NICHD）和多学科分子和生理学合作伙伴，我们将提出以下假设：1）炎症的组合，激素和转录血浆标记物可用于区分女性是否患有子宫内膜异位症; 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可以进一步细化子宫内膜标志物演示和参与者特征。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制定生物样本库协调项目（WERF-EPHect）。他们总共有近 2000 名患有或未患有子宫内膜异位症并具有注释良好的表型数据和血液样本。在患有子宫内膜异位症的女性中，我们现有 300 多个注释良好的异位子宫内膜样本。相关性：子宫内膜异位症的信息亚型的发现以及导致子宫内膜异位症的疾病分类子宫内膜异位症精准无创诊断工具及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，并可能导致患有子宫内膜异位症的女性的经济和个人费用。利用我们具有专业知识的多学科团队在生物标志物、子宫内膜异位症异质性和流行病学方面，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、精准治疗发展。