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.

项目摘要/摘要 子宫内膜异位症是一种常见且知识熟悉的疾病，影响了世界各地数百万妇女。这 对生育能力和骨盆疼痛的影响估计要花费220亿美元，但这不包括成本 治疗IBS，间质性膀胱炎和失败的辅助生殖技术（ART）周期的成本。这是 估计有40％的ART周期是由于未诊断的子宫内膜异位症而引起的，大多数妇女承诺 艺术从未经过测试。该建议基于既定技术，该技术检测 子宫内膜异位症。根据已发表的结果，过表达癌基因BCL6的妇女的妇女为47％ 与正常BCL6的女性相比，活产生率降低。该建议将开发这项技术， 验证这些发现并采用侵入性较小的测试格式。目标包括第一阶段的目标 验证并检查在子宫内膜异位症病例中存在的第二个共表达生物标志物，Sirtuin 1（SIRT1） 子宫内膜异位症的女性月经周期的所有阶段。第一阶段也将研究 SIRT1和BCL6在包括血液，唾液，尿液和颈粘的替代组织中的表达 使用ELISA技术。第二阶段的目的将研究BCl6和/或SIRT1的表达作为预测指标 在主要的IVF中心的怀孕结局。在对sirt1/bcl6呈阳性的女性中 子宫内膜异位症，第二次多中心研究将检查是否抑制子宫内膜异位症与新颖的， 新认可的GnRH激动剂（Elagolix）随后进行胚胎转移将改善预后。最后，团队 将开发，验证和商业化用于子宫内膜异位和子宫内膜的参考实验室测试 基于I期结果，使用较少的侵入性方法测量SIRT或BCL6的接受度。决赛 参考实验室测试的验证将涉及腹腔镜检查之前的前瞻性测试或 不孕症（病例和不育对照）以及经过管结扎的生育能力的妇女 灭菌（肥沃对照）。采用这种方法，灵敏度，特异性以及负面和积极的预测性 值可以定义。该项目的目标是建立一个经过验证的新的，侵入性的较少，测试 到2021年子宫内膜异位症，这将使所有治疗妇女的医生都缩短诊断时间 在各种临床环境中的子宫内膜异位症，包括骨盆疼痛，不育症，肠易激综合症和其他 骨盆投诉。