SIRT1 and BCL6: Dual Biomarkers of Endometriosis and Endometrial Receptivity

项目摘要/摘要 子宫内膜异位症是一种常见但知之甚少的疾病，影响着世界各地数百万女性。这个 对生育能力和盆腔疼痛的影响估计要花费220亿美元，但这还不包括 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。它是 据估计，40%的失败的抗逆转录病毒治疗周期是由于未诊断的子宫内膜异位症，大多数妇女接受了 艺术从未经受过考验。这项建议基于成熟的技术，该技术可以检测到 子宫内膜异位症。根据公布的结果，癌基因bcl6过度表达的女性有47%的风险。 与BCL6正常的妇女相比，活产率降低。这项提议将发展这项技术， 验证这些发现，并寻求一种侵入性更小的测试模式。目标包括第一阶段的目标，该阶段将 验证和检测第二个共表达的生物标志物Sirtuin 1(SIRT1)在子宫内膜异位症病例中的存在 记录在案的子宫内膜异位症患者月经周期的所有阶段。这一第一阶段还将研究 SIRT1和BCL6在血液、唾液、尿液和宫颈粘液等组织来源中的表达 采用酶联免疫吸附试验技术。第二阶段的AIMS将检测BCL6和/或SIRT1的表达作为预测 妊娠结局在一家主要的试管受精中心。SIRT1/BCL6检测呈阳性的女性 第二项多中心研究将检查是否有一种新的抑制子宫内膜异位症的方法， 新批准的促性腺激素释放激素激动剂(Elagolix)和胚胎移植将改善预后。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 根据第一阶段的结果，使用侵入性较小的方法测量SIRT或BCL6的接受性。决赛 参考实验室测试的验证将包括在腹腔镜检查前对盆腔疼痛或 不孕症(病例和不孕对照)和接受输卵管结扎术的女性永久 绝育(生育控制)。用这种方法，灵敏度、特异度、阴性和阳性预测 价值可以被定义。该项目的目标是建立一种经过验证的、侵入性较小的新测试，用于 到2021年，将允许所有治疗女性的医生缩短诊断为子宫内膜异位症的时间 各种临床情况下的子宫内膜异位症，包括盆腔疼痛、不孕不育、肠易激综合征等 盆腔不适。

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.