SIRT1 and BCL6: Dual Biomarkers of Endometriosis and Endometrial Receptivity

SIRT1 和 BCL6：子宫内膜异位症和子宫内膜容受性的双重生物标志物

• 批准号: 10028286
• 负责人: Dan Angress
• 金额: $ 51.28万
• 依托单位: CICERODX, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10028286
• 关键词: Affect; Agonist; Archives; Assisted Reproductive Technology; BCL6 gene; Benign; Biological Markers; Biopsy; Birth Rate; Blood; Cervical; Characteristics; Clinical; Consensus; Data; Development; Diagnosis; Diagnostic tests; Disease; Dysmenorrhea; Early Diagnosis; Embryo Transfer; Endometrial; Enzyme-Linked Immunosorbent Assay; Estrogens; Evaluation; Failure; Fertility; Functional disorder; Future; GNRH1 gene; Goals; Gonadotropin Releasing Hormone Inhibitor; Health Care Costs; Hormones; Individual; Infertility; Inflammation; International; Interstitial Cystitis; Intervention; Irritable Bowel Syndrome; Laboratories; Laparoscopy; Lesion; Live Birth; Marketing; Measures; Menstrual cycle; Methods; Mucous body substance; Multicenter Studies; Oncogenes; Operative Surgical Procedures; Oral; Oral Contraceptives; Outcome; Pain; Patients; Pelvic Pain; Pelvis; Phase; Physicians; Population; Predictive Value; Pregnancy; Pregnancy Outcome; Prevalence; Progesterone; Prospective Studies; Proteins; Publishing; Recurrence; Role; SIRT1 gene; Saliva; Sensitivity and Specificity; Source; Sterilization; Symptoms; Technology; Testing; Time; Tissues; Translating; Treatment outcome; Tubal Ligation; Urine; Validation; Woman; aged; base; chronic pelvic pain; clinical application; clinically relevant; cost; diagnosis evaluation; endometriosis; endometriosis-related infertility; experience; idiopathic infertility; improved; improved outcome; novel; outcome prediction; overexpression; performance tests; proliferative phase Menstrual cycle; prospective; prospective test; protein biomarkers; reproductive; research clinical testing; specific biomarkers; success

PROJECT SUMMARY/ABSTRACT Endometriosis is a common and poorly understood disease affecting millions of women around the world. The impact on fertility and pelvic pain is estimated to cost $22 billion dollars, but this does not include the costs to treat IBS, interstitial cystitis and the cost of failed Assisted Reproductive Technology (ART) cycles. It is estimated that 40% of failed ART cycles are due to undiagnosed endometriosis, and most women undertaking ART have never been tested. This proposal is based on established technology that detects all stages of endometriosis. Based on published results, women who over-express the oncogene BCL6 have a 47% reduction in live birth rate compared to women with normal BCL6. This proposal will develop this technology, validate these findings and pursue a less invasive test format. Aims including those in Phase I, which will validate and examine a second co-expressed biomarker, Sirtuin 1 (SIRT1) present in endometriosis cases at all phases of the menstrual cycle in women with documented endometriosis. This first phase will also study expression of SIRT1 and BCL6 in alternative tissue sources including blood, saliva, urine, and cervical mucous using ELISA technology. Aims in Phase II will examine expression of BCL6 and/or SIRT1 as predictors of pregnancy outcomes in at a major IVF center. In women who test positive for SIRT1/BCL6 with suspected endometriosis, a second multi-center study will examine whether suppression of endometriosis with a novel, newly approved GnRH agonist (Elagolix) followed by embryo transfer will improve outcomes. Finally, the team will develop, validate, and commercialize a reference laboratory test for endometriosis and endometrial receptivity using less invasive approaches for measuring SIRT or BCL6 based on Phase I results. The final validation of a reference laboratory test will involve prospective testing before laparoscopy for pelvic pain or infertility (cases and infertile controls) and for women with fertility undergoing tubal ligation for permanent sterilization (fertile controls). With this approach the sensitivity, specificity, and negative and positive predictive value can be defined. The goal for this project is to establish a validated new, less invasive, test for endometriosis by 2021 that will allow all physicians treating women to shorten the time to diagnosis for endometriosis in a variety of clinical settings including pelvic pain, infertility, irritable bowel syndrome and other pelvic complaints.

项目总结/摘要 子宫内膜异位症是一种常见且知之甚少的疾病，影响着全世界数百万妇女。的 对生育能力和骨盆疼痛的影响估计要花费220亿美元，但这不包括 治疗肠易激综合征、间质性膀胱炎和辅助生殖技术（ART）周期失败的费用。是 据估计，40%的ART周期失败是由于未诊断的子宫内膜异位症， ART从未被测试过。该提案基于现有技术，该技术可检测所有阶段的 子宫内膜异位症根据已发表的结果，过度表达癌基因BCL 6的女性有47%的 与BCL正常的妇女相比，活产率降低6。这项提案将发展这项技术， 验证这些发现，并寻求一种侵入性较小的测试形式。目标包括第一阶段的目标， 验证和检查第二个共表达的生物标志物，Sirtuin 1（SIRT 1）存在于子宫内膜异位症病例中， 子宫内膜异位症患者月经周期的所有阶段。第一阶段还将研究 SIRT 1和BCL 6在血液、唾液、尿液和宫颈粘膜等替代组织来源中的表达 ELISA技术。第二阶段的目标是检查BCL 6和/或SIRT 1的表达， 在一家大型IVF中心的妊娠结果。在SIRT 1/BCL 6检测呈阳性的女性中， 子宫内膜异位症，第二个多中心研究将检查是否抑制子宫内膜异位症与一种新的， 新批准的GnRH激动剂（Elagolix）随后进行胚胎移植将改善结局。最后，团队 将开发，验证和商业化子宫内膜异位症和子宫内膜异位症的参考实验室测试 基于I期结果，使用侵入性较小的方法测量SIRT或BCL 6的感受性。最终 参考实验室检查的验证将涉及腹腔镜检查前盆腔疼痛的前瞻性检查， 不孕症（病例和不孕症对照）和接受输卵管结扎术的生育妇女 绝育（生育对照）。通过这种方法，灵敏度，特异性，阴性和阳性预测 值可以定义。该项目的目标是建立一个有效的新的，侵入性较小的测试， 到2021年，子宫内膜异位症将允许所有治疗女性的医生缩短诊断时间， 子宫内膜异位症在各种临床情况下，包括盆腔疼痛，不孕症，肠易激综合征和其他 骨盆不适