The non-invasive early detection of endometriosis

摘要 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。近一半的受影响妇女患有慢性盆腔疼痛， 其中70%的患者在月经期间疼痛。性交疼痛（“性交困难”）和不孕症发生在 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。由于这种方法的侵入性， 子宫内膜异位症的诊断和治疗相当延迟，从症状发作到 诊断为10年。这种显著延迟的后果是延长和进行性疼痛， 不孕症和相当大的社会/经济影响。 本研究的目的是发展子宫内膜异位症的早期无创性筛查方法。 具体来说，我们将靶向细胞外DNA循环片段携带的DNA甲基化特征， 在本文中称为无细胞DNA（cfDNA）。这些碎片在各种流体储层中被检测到， 包括血浆，传递关于它们的细胞类型起源及其病理学的表观基因组信息。 状态我们的过度假设是，子宫组织中DNA甲基化特征的改变， 子宫内膜异位症患者可通过分析血浆来源的cfDNA检测。在这项研究中，我们将建立一个 初步数据的基础，以发展早期非侵入性检测方法， 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.