The non-invasive early detection of endometriosis

子宫内膜异位症的非侵入性早期检测

• 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
• 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

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，涉及子宫内膜腺体和子宫外基质的生长。 主要症状是盆腔疼痛和不孕症，近一半受影响的女性患有慢性盆腔疼痛。 其中 70% 的疼痛发生在月经期间（“性交疼痛”），而不孕则发生在月经期间。 近一半的女性患有子宫内膜异位症，不太常见的症状包括泌尿或肠道症状。 大约 25% 的女性没有任何症状。子宫内膜异位症可能会产生社会和心理影响。 目前，明确的诊断是通过手术活检来实现的，由于这种方法的侵入性， 子宫内膜异位症的诊断和治疗明显延迟，从症状出现到出现症状的平均时间 这种显着延迟的后果是长期且进行性疼痛，存在以下风险： 不孕不育和相当大的社会/经济影响。 本研究的目的是开发早期发现子宫内膜异位症的非侵入性筛查方法。 具体来说，我们将针对细胞外 DNA 循环片段携带的 DNA 甲基化特征， 这些片段在本文中称为无细胞 DNA (cfDNA)，可在各种流体储存器中检测到。 包括血浆，传达有关其细胞类型起源及其病理的表观基因组信息 我们的首要假设是子宫组织中的 DNA 甲基化特征发生了改变。 子宫内膜异位症患者可以通过血浆来源的 cfDNA 分析来检测。 为开发早期非侵入性检测方法奠定初步数据基础 子宫内膜异位症。