Development of a serum biosignature for ectopic pregnancy.

异位妊娠血清生物特征的开发。

• 批准号: 8846129
• 负责人: Kurt T Barnhart
• 金额: $ 66.18万
• 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/8846129
• 关键词: Basic Science; Beer; Biological Assay; Biological Markers; Blood; Case-Control Studies; Cause of Death; Chorionic villi; Clinical; Clinical Management; Cohort Studies; Complication; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Discipline of obstetrics; Disease; Early Diagnosis; Ectopic Pregnancy; Epidemiology; Failure; First Pregnancy Trimester; Goals; Gynecology; Health; Hemorrhage; Human Chorionic Gonadotropin; 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; Proteomics; Protocols documentation; Public Health; Research; Resources; Risk; Rupture; Series; Serum; Specimen; Spontaneous abortion; Symptoms; Testing; Translating; Ultrasonography; Woman; base; biosignature; clinical application; clinically significant; corpus luteum; implantation; improved; maternal morbidity; mortality; multidisciplinary; novel marker; patient population; prospective; 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)：这是一个高生产力、多学科、多中心项目的修订申请，评估有宫外孕(EP)和早期妊娠失败风险的妇女的诊断。早期妊娠失败是妊娠中最常见的并发症，估计有25%的临床公认的妊娠以流产告终，1-2%被诊断为异位妊娠(EP)。EP是与妊娠有关的主要死亡原因，也是导致孕产妇发病率的主要因素。当超声看不到妊娠时，区分健康的宫内妊娠(IUP)和流产或EP是一个关键的临床挑战，因为没有其他明确的、非侵入性的诊断测试。目前的诊断方案可能导致所需IUP的中断和/或与EP破裂相关的发病率。我们已经证明，当联合使用EP时，EP的一些可能的生物标志物可以区分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记物，其中一个我们已经验证：ADAM-12。该项目的目标是扩大生物标志物的使用，以开发一种区分EP、正在进行的IUP和流产的生物签名。具体目的和方法：我们计划开发一种多标记物生物签名图谱来辅助EP的诊断。我们假设，少量的标记物结合使用，将能够区分EP和IUP(正在进行的IUP和流产的组合)和/或可以用来区分不可行的妊娠(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、改进和验证一种血清(多标记物)试验，以基于早期植入和生存能力的推定标记物来鉴定EP。在具体目标2中，我们将验证新发现的EP生物标记物的潜力，以补充(或取代)我们目前的多标记小组中的那些生物标记物。在具体目标3中，我们将进行一项无偏见的三向蛋白质组发现研究，该研究将识别区分EP、IUP和流产的新的、低丰度的生物标志物候选。摘要：这项建议是一个独特的机会，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健康后果的生殖疾病的能力方面的重要限制。利用获得大量地理、种族和人种不同的EP风险女性的机会，我们计划使用良好的表型生物标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，以评估预期患者群体的实际使用情况。非侵入性诊断方法的发展，如高精度诊断EP和/或流产的血清试验，将产生巨大的临床影响。