Development of a serum biosignature for ectopic pregnancy.

异位妊娠血清生物特征的开发。

• 批准号: 9473793
• 负责人: Kurt T Barnhart
• 金额: $ 65.34万
• 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 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9473793
• 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; early pregnancy; 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）：这是一项经过修订的申请，来自高生产力，多学科的多中心项目，评估了处于异位妊娠风险（EP）和早期妊娠衰竭风险的妇女的诊断。 早期妊娠衰竭是妊娠中最常见的并发症，估计有25％的临床认可的怀孕在流产中结束，而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，也是孕产妇发病率的主要贡献者。当超声检查妊娠不可见时，将健康持续的宫内妊娠（IUP）与流产或EP区分开，或者EP会带来关键的临床挑战，因为没有其他明确的无创诊断测试。当前的诊断方案可能导致与EP破裂有关的所需IUP和/或发病率的中断。我们已经证明，当组合使用时，许多EP的假定生物标志物可以将IUP与EP区分开。 使用公正的蛋白质组学分析方法，我们还建立了新的生物标志物，我们已经验证了它：Adam-12。 该项目的目的是扩大生物标志物的使用来开发区分EP，正在进行的IUP和流产的生物签名。 具体目的和方法：我们计划开发多个标记生物签名曲线以帮助诊断EP。 我们假设组合使用的少数标​​记将能够将EP与IUP区分开（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Miscarriage的组合）正在进行的IUP。在特定目标1中，我们将根据假定的早期植入和生存能力来开发，完善和验证血清（多重标记）测试以识别EP。 在特定的目标2中，我们将验证EP新发现的生物标志物的潜力增加（或替换）当前多重标记面板中的生物标志物。在特定目标3中，我们将进行一项公正的三向蛋白质组学发现研究，该研究将确定区分EP，IUP和流产的新的，较低的丰度生物标志物候选者。 摘要：该提案代表了将流行病学和基础科学方法结合起来的独特机会，以了解和改善我们诊断和治疗具有重要公共健康后果的生殖障碍能力的重要局限性。利用访问大量的地理，种族和种族多元化的女性，我们计划使用良好的表型生物特异性人物进行一系列多中心案例对照研究，并最终进行一项前瞻性同类研究，以评估实际使用预期的患者人群。 非侵入性诊断方法的开发，例如以高准确性诊断EP和/或流产的血清测试将产生巨大的临床影响。

项目成果

Identification and verification of plasma protein biomarkers that accurately identify an ectopic pregnancy.

• DOI: 10.1186/s12014-023-09425-w
• 发表时间: 2023-09-15
• 期刊: CLINICAL PROTEOMICS
• 影响因子: 3.8
• 作者: Beer, Lynn A.;Yin, Xiangfan;Ding, Jianyi;Senapati, Suneeta;Sammel, Mary D.;Barnhart, Kurt T.;Liu, Qin;Speicher, David W.;Goldman, Aaron R.
• 通讯作者: Goldman, Aaron R.

Perinatal Outcomes of Pregnancies of Unknown Location With Human Chorionic Gonadotropin Concentration Above the Discriminatory Zone.

• DOI: 10.1097/aog.0000000000004939
• 发表时间: 2022-11-01
• 期刊: Obstetrics and gynecology
• 影响因子: 7.2

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

应用多重平台识别妊娠位置和活力的新型生物标志物。

• DOI: 10.21203/rs.3.rs-2777020/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Lee,IrisTien-Lynn;Senapati,Suneeta;Schreiber,Courtney;Koelper,Nathanael;Takacs,Peter;Barnhart,Kurt
• 通讯作者: Barnhart,Kurt

Sensitivity and specificity of placental proteins for gestational age screening: An exploratory study.

胎盘蛋白用于胎龄筛查的敏感性和特异性：一项探索性研究。

• DOI: 10.1016/j.contraception.2020.01.007
• 发表时间: 2020
• 期刊: Contraception
• 影响因子: 2.9
• 作者: Raymond,ElizabethG;Frye,LauraJ;Weaver,MarkA;Lebed,JoelP;Ren,Xiangdong;Steider,Elizabeth;Winikoff,Beverly;Barnhart,KurtT
• 通讯作者: Barnhart,KurtT