The non-invasive early detection of endometriosis

摘要 子宫内膜异位症是一种衰弱的疾病，涉及子宫内膜腺和子宫外间质的生长。 主要症状是盆腔疼痛和不孕不育。近一半受影响的女性患有慢性盆腔疼痛， 在其中70%的患者中，疼痛发生在月经期间。性交疼痛(“性交困难”)和不孕症发生在 近一半的妇女患有子宫内膜异位症。不太常见的症状包括排尿或肠道症状。 大约25%的女性没有任何症状。子宫内膜异位症可能会对社会和心理产生影响。 目前，明确的诊断是通过手术活检实现的。由于这种方法具有侵入性，因此 子宫内膜异位症的诊断和治疗有相当大的延迟，从症状出现到 诊断时间为10年。这一重大延误的后果是延长和进行性疼痛，有 不孕症和相当大的社会/经济影响。 本研究旨在为子宫内膜异位症的早期诊断提供无创性的筛查方法。 具体地说，我们将针对细胞外DNA循环片段携带的DNA甲基化特征， 在此称为无细胞DNA(CfDNA)。这些碎片在各种流体储集层中被检测到 包括血浆，传递关于它们的细胞来源类型及其病理的表观基因组信息 州政府。我们最重要的假设是，子宫组织中DNA甲基化信号的改变 子宫内膜异位症患者可通过分析血浆来源的cfDNA进行检测。在本研究中，我们将构建一个 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。

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.