The non-invasive early detection of endometriosis

子宫内膜异位症的非侵入性早期检测

基本信息

批准号：
10574971
负责人：
David Gerard Peters
金额：
$ 21.96万
依托单位：
MAGEE-WOMEN'S RES INST AND FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10574971
关键词：
Affect Age Anatomy Area Biology Biopsy Blood Tests Chronic Disease Clear Cell Complex DNA DNA Methylation DNA methylation profiling Data Detection Development Diagnosis Diagnostic Disease Disease Progression Dysmenorrhea Dyspareunia Early Diagnosis Endometrial Endometrium Foundations Genetic Germ-Line Mutation Gland Goals Growth Gynecologic Health High Risk Woman Hospitalization Hysterectomy Infertility Intervention Intestines Laparoscopic Surgical Procedures Laparoscopy Liquid substance Location Malignant neoplasm of ovary Menarche Menopause Menstruation Methods Nature Non-Invasive Detection Oncology Onset of illness Operative Surgical Procedures Pain Pathologic Patients Pelvic Pain Personal Satisfaction Phenotype Plasma Postmenopause Quality of life Risk Sampling Screening procedure Serous Somatic Mutation Symptoms Testing Time Tissue Sample Tissues Uterus Woman cell free DNA cell type chronic pelvic pain common symptom cost cost effective disease diagnosis disease phenotype economic impact effective therapy endometriosis epigenomics experience extracellular genome-wide genome-wide analysis improved liquid biopsy method development novel novel diagnostics novel therapeutics psychologic reproductive screening sex social tool urinary young woman

Affect Age Anatomy Area Biology Biopsy Blood Tests Chronic Disease Clear Cell Complex DNA DNA Methylation DNA methylation profiling Data Detection Development Diagnosis Diagnostic Disease Disease Progression Dysmenorrhea Dyspareunia Early Diagnosis Endometrial Endometrium Foundations Genetic Germ-Line Mutation Gland Goals Growth Gynecologic Health High Risk Woman Hospitalization Hysterectomy Infertility Intervention Intestines Laparoscopic Surgical Procedures Laparoscopy Liquid substance Location Malignant neoplasm of ovary Menarche Menopause Menstruation Methods Nature Non-Invasive Detection Oncology Onset of illness Operative Surgical Procedures Pain Pathologic Patients Pelvic Pain Personal Satisfaction Phenotype Plasma Postmenopause Quality of life Risk Sampling Screening procedure Serous Somatic Mutation Symptoms Testing Time Tissue Sample Tissues Uterus Woman cell free DNA cell type chronic pelvic pain common symptom cost cost effective disease diagnosis disease phenotype economic impact effective therapy endometriosis epigenomics experience extracellular genome-wide genome-wide analysis improved liquid biopsy method development novel novel diagnostics novel therapeutics psychologic reproductive screening sex social tool urinary young woman

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项目摘要

ABSTRACT Endometriosis is a debilitating disease involving the growth of endometrial glands and stroma outside the uterus. The primary symptoms are pelvic pain and infertility. Nearly half of affected women have chronic pelvic pain, and in 70% of those, the pain occurs during menstruation. Pain with sex (“dyspareunia”) and infertility occur in close to half of women affected by endometriosis. Less common symptoms include urinary or bowel symptoms. About 25% of women have no symptoms. Endometriosis can have both social and psychological effects. Currently, definitive diagnosis is achieved by surgical biopsy. Because of the invasive nature of this method, the diagnosis and treatment of endometriosis is considerably delayed, with average time from symptom onset to diagnosis being 10 years. The consequence of this significant delay is prolonged and progressive pain, a risk of infertility and considerable social/economic impact. The purpose of this study is to develop non-invasive screening methods for the early detection of endometriosis. Specifically, we will target DNA methylation signatures carried by circulating fragments of extracellular DNA, referred to herein as cell-free DNA (cfDNA). These fragments, which are detected in a variety of fluid reservoirs including blood plasma, convey epigenomic information both about their cell type of origin and its pathological state. Our over-arching hypothesis is that altered DNA methylation signatures in the uterine tissue of endometriosis patients are detectable via analysis of plasma-derived cfDNA. In this study we will build a foundation of preliminary data towards the development of methods for the early non-invasive detection of endometriosis.

抽象的子宫内膜异位症是一种使人衰弱的疾病，涉及子宫外子宫内膜和基质的生长。主要症状是骨盆疼痛和不育。近一半的受影响女性患有慢性骨盆疼痛，在其中70％的人中，疼痛发生在月经期间。性疼痛（“全疾病困难”）和不育发生在接近子宫内膜异位症影响的妇女中有近一半。较不常见的症状包括尿路或肠症状。约25％的女性没有症状。子宫内膜异位症可能具有社会和心理影响。目前，通过手术活检来实现确定性诊断。由于这种方法的侵入性，人们认为子宫内膜异位症的诊断和治疗被认为会延迟，而平均时间从症状发作到诊断是10年。这种重大延迟的后果是长时间和渐进的疼痛，这是不孕症和相当大的社会/经济影响。这项研究的目的是开发非侵入性筛查方法以早期检测子宫内膜异位症。具体而言，我们将针对通过细胞外DNA的循环片段携带的DNA甲基化特征，此处称为无细胞DNA（CFDNA）。这些碎片，在各种流体库中检测到包括血浆，传达有关其细胞形式及其病理的表观基因组信息状态。我们的架构假设是，在子宫组织中的DNA甲基化特征改变了子宫内膜异位症患者可通过分析血浆衍生的CFDNA检测。在这项研究中，我们将建立一个初步数据的基础，用于开发早期非侵入性检测方法的基础子宫内膜异位症。