Development of a serum biosignature for ectopic pregnancy.

异位妊娠血清生物特征的开发。

• 批准号: 9268010
• 负责人: Kurt T Barnhart
• 金额: $ 65.99万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-07 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268010
• 关键词: Basic Science; Beer; Biological Assay; Biological Markers; Blood; Case-Control Studies; Cause of Death; Chorionic villi; Clinical; Clinical Management; Complication; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Discipline of obstetrics; Disease; Early Diagnosis; Ectopic Pregnancy; Epidemiology; Failure; First Pregnancy Trimester; Geography; Goals; Gynecology; Hemorrhage; Human Chorionic Gonadotropin; Iatrogenesis; Interruption; Location; Mammalian Oviducts; Measurement; Medicine; Methodology; Methods; Morbidity - disease rate; Outcome; Pain; Pathway interactions; Performance; Phenotype; Population; Pregnancy; Pregnant Women; Prenatal Diagnosis; Procedures; Process; Prospective cohort study; Proteomics; Protocols documentation; Public Health; Research; Resources; Risk; Rupture; Series; Serum; Specimen; Spontaneous abortion; Symptoms; Testing; Translating; Ultrasonography; Woman; base; biomarker panel; biosignature; candidate marker; clinical application; clinically significant; corpus luteum; ethnic diversity; implantation; improved; maternal morbidity; mortality; multidisciplinary; noninvasive diagnosis; novel marker; patient population; potential biomarker; public health relevance; racial diversity; reproductive

DESCRIPTION (provided by applicant): This is a revised application from a highly productive, multidisciplinary, multicenter project evaluating the diagnosis of women at risk for ectopic pregnancy (EP) and early pregnancy failure. Early pregnancy failure is the most common complication in pregnancy with an estimated 25% of clinically recognized pregnancies ending in miscarriage, and 1-2% are diagnosed as ectopic pregnancy (EP). EP is the leading pregnancy-related cause of death and a major contributor to maternal morbidity. When the gestation is not visible with ultrasound, distinguishing a healthy ongoing intrauterine gestation (IUP) from a miscarriage or an EP poses a critical clinical challenge as there is no other definitive, noninvasive diagnostic test. Current diagnostic protocols can result in the interruption of a desired IUP and/or morbidity associated with rupture of an EP. We have demonstrated that a number of putative biomarkers of EP can distinguish IUP from EP when used in combination. Using an unbiased proteomic analysis approach we have also established new biomarkers, one which we have already validated: ADAM-12. The goal of this project is to expand the use of biomarkers to develop a biosignature distinguishing EP, ongoing IUP and miscarriage. Specific Aims and Methods: We plan to develop a multiple marker bio-signature profile to aid in the diagnosis of EP. We hypothesize that a small number of markers, used in combination, will be able to distinguish an EP from IUP (combination of ongoing IUP and miscarriage) and/or can be used to distinguish a nonviable gestation (combination of EP and miscarriage) from an ongoing IUP. In Specific aim 1 we will develop, refine and validate a serum (multiple marker) test to identify EP based on putative markers of early implantation and viability. In Specific Aim 2 we will validate the potential of newly discovered biomarkers of EP to add to (or replace) those in our current multiple marker panel. In Specific aim 3 we will conduct an unbiased three-way proteomic discovery study that will identify new, lower abundance biomarker candidates that distinguish between EP, IUP and miscarriage. Summary: This proposal represents a unique opportunity to combine epidemiologic and basic science methodologies to understand and improve upon important limitations in our ability to diagnose and treat a reproductive disorder with important public health consequences. Utilizing access to a large number of geographically, racially and ethnically diverse women at risk for EP, we plan to conduct a series of multicenter case control studies using well phenotyped bio-specimens, and ultimately conduct a prospective cohort study to assess actual use in the intended patient population. The development of non invasive methods of diagnosis, such as a serum test to diagnose an EP and/or miscarriage with high accuracy, would have tremendous clinical impact.

描述（由申请人提供）：这是一个高产、多学科、多中心项目的修订申请，该项目评估对有宫外孕 (EP) 和早期妊娠失败风险的女性的诊断。 早期妊娠失败是妊娠中最常见的并发症，估计临床认可的妊娠中有 25% 以流产告终，其中 1-2% 被诊断为宫外孕 (EP)。 EP 是与妊娠相关的主要死亡原因，也是孕产妇发病的主要原因。当超声无法看到妊娠时，区分健康的持续宫内妊娠 (IUP) 与流产或 EP 会带来严峻的临床挑战，因为没有其他明确的、无创的诊断测试。当前的诊断方案可能会导致所需的 IUP 中断和/或与 EP 破裂相关的发病率。我们已经证明，一些假定的 EP 生物标志物联合使用时可以区分 IUP 和 EP。 使用无偏见的蛋白质组分析方法，我们还建立了新的生物标志物，我们已经验证了这一标志物：ADAM-12。 该项目的目标是扩大生物标志物的使用，以开发区分 EP、正在进行的 IUP 和流产的生物特征。 具体目标和方法：我们计划开发多标记生物特征谱来帮助诊断 EP。 我们假设，组合使用少量标记物将能够区分 EP 和 IUP（正在进行的 IUP 和流产的组合）和/或可以用于区分无法存活的妊娠（EP 和流产的组合）和正在进行的 IUP。在具体目标 1 中，我们将开发、完善和验证血清（多标记）测试，以根据早期植入和活力的推定标记来识别 EP。 在具体目标 2 中，我们将验证新发现的 EP 生物标志物添加（或替换）我们当前多标志物组中的生物标志物的潜力。在具体目标 3 中，我们将进行一项公正的三向蛋白质组学发现研究，该研究将识别新的、较低丰度的候选生物标志物，以区分 EP、IUP 和流产。 摘要：该提案提供了一个独特的机会，可以将流行病学和基础科学方法结合起来，以了解和改进我们诊断和治疗具有重要公共卫生后果的生殖疾病的能力的重要局限性。利用大量具有 EP 风险的不同地域、种族和民族的女性，我们计划使用表型良好的生物样本进行一系列多中心病例对照研究，并最终进行前瞻性队列研究，以评估在目标患者群体中的实际使用情况。 非侵入性诊断方法的发展，例如高精度诊断 EP 和/或流产的血清检测，将产生巨大的临床影响。