Samuel Parry1, Heping Zhang2, Joseph Biggio3, Radek Bukowski4, Michael Varner5, Yaji Xu2, William W Andrews3, George R Saade4, M Sean Esplin5, Rita Leite6, John Ilekis7, Uma M Reddy7, Yoel Sadovsky8, Ian A Blair9. 1. Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA. Electronic address: parry@mail.med.upenn.edu. 2. Collaborative Center for Statistics in Science, Yale University School of Public Health, New Haven, CT. 3. Department of Obstetrics and Gynecology, University of Alabama, Birmingham, School of Medicine, Birmingham, AL. 4. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX. 5. Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT. 6. Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA. 7. Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD. 8. Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA. 9. Center for Cancer Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA.
Abstract
OBJECTIVE: We sought to identify serum biomarkers of early spontaneous preterm birth (SPTB) using semiquantitative proteomic analyses. STUDY DESIGN: This was a nested case-control study of pregnant women with previous SPTB. Maternal serum was collected at 19-24 and 28-32 weeks' gestation, and analyzed by liquid chromatography-multiple reaction monitoring/mass spectrometry. Targeted and shotgun proteomics identified 31 candidate proteins that were differentially expressed in pooled serum samples from spontaneous preterm (cases [<34 weeks]) and term (controls) deliveries. Candidate protein expression was compared in individual serum samples between cases and controls matched by age and race groups, and clinical site. Protein expression was verified by Western blot in the placenta and fetal membranes from cases and controls. RESULTS: Serum samples were available for 35 cases and 35 controls at 19-24 weeks, and 16 cases and 16 controls at 28-32 weeks. One protein, serpin B7, yielded serum concentrations that differed between cases and controls. The mean concentration of serpin B7 at 28-32 weeks was 1.5-fold higher in women with subsequent preterm deliveries compared to controls; there was no difference at 19-24 weeks. Higher levels of serpin B7 at both gestational age windows were associated with a shorter interval to delivery, and higher levels of serpin B7 in samples from 28-32 weeks were associated with a lower gestational age at delivery. Western blotting identified serpin B7 protein in placenta, amnion, and chorion from cases and controls. CONCLUSION: Targeted and shotgun serum proteomics analyses associated 1 protein, serpin B7, with early SPTB. Our results require validation in other cohorts and analysis of the possible mechanistic role of serpin B7 in parturition.
OBJECTIVE: We sought to identify serum biomarkers of early spontaneous preterm birth (SPTB) using semiquantitative proteomic analyses. STUDY DESIGN: This was a nested case-control study of pregnant women with previous SPTB. Maternal serum was collected at 19-24 and 28-32 weeks' gestation, and analyzed by liquid chromatography-multiple reaction monitoring/mass spectrometry. Targeted and shotgun proteomics identified 31 candidate proteins that were differentially expressed in pooled serum samples from spontaneous preterm (cases [<34 weeks]) and term (controls) deliveries. Candidate protein expression was compared in individual serum samples between cases and controls matched by age and race groups, and clinical site. Protein expression was verified by Western blot in the placenta and fetal membranes from cases and controls. RESULTS: Serum samples were available for 35 cases and 35 controls at 19-24 weeks, and 16 cases and 16 controls at 28-32 weeks. One protein, serpin B7, yielded serum concentrations that differed between cases and controls. The mean concentration of serpin B7 at 28-32 weeks was 1.5-fold higher in women with subsequent preterm deliveries compared to controls; there was no difference at 19-24 weeks. Higher levels of serpin B7 at both gestational age windows were associated with a shorter interval to delivery, and higher levels of serpin B7 in samples from 28-32 weeks were associated with a lower gestational age at delivery. Western blotting identified serpin B7 protein in placenta, amnion, and chorion from cases and controls. CONCLUSION: Targeted and shotgun serum proteomics analyses associated 1 protein, serpin B7, with early SPTB. Our results require validation in other cohorts and analysis of the possible mechanistic role of serpin B7 in parturition.
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