Developing a non-invasive, definitive diagnostic for endometriosis using biomarkers in menstrual effluence

利用月经排出物中的生物标志物开发子宫内膜异位症的非侵入性、明确诊断方法

• 批准号: 10547989
• 负责人: Stephen Gire
• 金额: $ 110.85万
• 依托单位: NEXTGENJANE, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10547989
• 关键词: Address; Affect; Algorithmic Analysis; Algorithms; Biological; Biological Markers; Blinded; Blood; Classification; Clinical; Collection; Complex; Confidence Intervals; Data; Databases; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Early Diagnosis; Early Intervention; Endometrial; Enrollment; Evaluation; Genomics; Goals; Gold; Histologic; Home; Hormones; Laboratories; Laparoscopic Surgical Procedures; Laparoscopy; Logistic Regressions; Medical; Menstrual fluid; Menstruation; Messenger RNA; Methods; MicroRNAs; Modeling; Nature; Operative Surgical Procedures; Patients; Performance; Periodicity; Phase; Population; Procedures; Prognosis; RNA; Recovery; Recurrence; Sampling; Sensitivity and Specificity; Signal Transduction; Source; Statistical Data Interpretation; Surveys; Symptoms; System; Tampons; Testing; Therapeutic Intervention; Time; Tissues; Validation; base; biomarker development; biomarker discovery; candidate marker; case control; classification algorithm; cost; diagnosis standard; disease classification; disease diagnosis; endometriosis; genomic biomarker; genomic signature; improved; meetings; noninvasive diagnosis; novel; novel marker; patient prognosis; predictive marker; prevent; recruit; reproductive; research study; sample collection; tool; transcriptome sequencing

Summary Endometriosis is a complex disease that on average, involves a ten-year gap between symptom onset and diagnosis. Moreover, due to the current surgical nature of endometriosis diagnosis (laparoscopy), research studies involving confirmed cases are both difficult to obtain and costly to recruit for. Laparoscopic surgery (recovery times 2-6 weeks) followed by histological confirmation is considered the gold standard for diagnosis. However, even with surgical intervention, 50% of patients have recurrence, underlining the fact that endometriosis shows periodic states of activation, regardless of surgical or therapeutic intervention. Consequently, a non-invasive, reliable biomarker test for endometriosis is a significant unmet medical need. A non-invasive diagnostic for endometriosis would motivate earlier detection of disease and could fundamentally change a patient’s prognosis by preventing disease progression. Menstrual fluid is a rich source of reproductive tissue that can be utilized for disease diagnosis. Next Gen Jane are developing a menstrual effluent competent collection tool, the Smart Tampon System (STS) which addresses issues of non-invasive sample accessibility and ease of sample transport to a laboratory. Toward development of a reliable biomarker for endometriosis, our preliminary data with the STS device indicates we can detect multiple RNA species in menstrual effluent, some of which have been previously discovered in other related studies. We believe that the STS provides unparalleled ease of access to menstrual effluent and markedly improves sample handling efficiencies. These factors alongside the demonstrated utility of the STS as a sample for RNASeq (amongst other studies) differentiates this proposal from other non-invasive approaches to detection of endometriosis. Our goal is to develop a non-invasive ”yes/no” diagnostic test for endometriosis by examining the genomic signatures of endometrial tissue shed into a tampon during menstruation. In order to further identify and evaluate the performance of genomic markers in menstrual fluid, we will enroll 72 patients with a negative or positive surgical confirmation of endometriosis in order to: Firstly, confirm previously identified biomarkers from pilot data that evaluates diagnosis of disease. Secondly, we will use statistical classification of RNASeq data to examine ~300 pre- and post- laparoscopy matched patient samples to confirm sensitivity and specificity of miRNA and mRNA biomarkers in concert with patient survey data.

概括 子宫内膜异位症是一种复杂的疾病，平均涉及症状发作和 诊断。此外，由于当前的子宫内膜异位诊断（腹腔镜检查）的手术性质，研究 涉及的研究确认案件既难以获得，也很难招募。腹腔镜手术 （恢复时间2-6周）随后进行组织学确认被认为是诊断的金标准。 但是，即使进行了手术干预，有50％的患者复发，这强调了这样一个事实，即 子宫内膜异位症显示出激活的周期状态，无论手术或治疗性干预如何。 因此，对子宫内膜异位症的非侵入性，可靠的生物标志物检测是一种巨大的未满足医疗需求。 子宫内膜异位症的非侵入性诊断将激发疾病的早期发现，并且可以从根本上进行 通过预防疾病进展来改变患者的预后。月经流体是繁殖的丰富来源 可用于疾病诊断的组织。下一代Jane正在开发月经有效的能力 收集工具，智能卫生棉条系统（STS），该系统解决了非侵入性样本可访问性问题 并易于运输到实验室的样品。 为了开发可靠的生物标志物用于子宫内膜异位症，我们使用STS设备的初步数据 表明我们可以检测到月经效率的多个RNA物种，其中一些以前是 在其他相关研究中发现。我们认为，STS提供了无与伦比的月经访问 效果并明显提高样品处理效率。这些因素沿证明的实用程序 STS作为RNASEQ的样本（除其他研究）将该提案与其他非侵入性区分开 检测子宫内膜异位症的方法。 我们的目标是通过检查基因组来开发子宫内膜异位症的非侵入性“是/否”诊断测试 月经期间，子宫内膜组织的签名脱落到尾ton中。为了进一步识别和评估 月经液中基因组标记的性能，我们将招募72例阴性或阳性患者 子宫内膜异位症的手术确认，以便：首先，确认先前从试验数据中鉴定出的生物标志物 评估疾病的诊断。其次，我们将使用RNASEQ数据的统计分类来检查 〜300次前后腹腔镜检查与患者样本相匹配，以确认miRNA的敏感性和特异性 mRNA生物标志物与患者调查数据一致。