Scott A Shainker1, Robert M Silver2, Anna M Modest3, Michele R Hacker3, Jonathan L Hecht4, Saira Salahuddin3, Simon T Dillon5, Erin J Ciampa6, Mary E Dalton7, Hasan H Otu8, Alfred Z Abuhamad9, Brett D Einerson2, D Ware Branch2, Blair J Wylie3, Towia A Libermann5, S Ananth Karumanchi10. 1. Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address: sshainke@bidmc.harvard.edu. 2. Department of Obstetrics and Gynecology, University of Utah Health School of Medicine, Salt Lake City, UT. 3. Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 4. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 5. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 6. Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 7. Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY. 8. Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE. 9. Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA. 10. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Abstract
INTRODUCTION: Many cases of placenta accreta spectrum (PAS) are not diagnosed antenatally, despite identified risk factors and improved imaging methods. Identification of plasma protein biomarkers could further improve antenatal diagnosis of PAS. OBJECTIVE: The purpose of this study was to determine if women with PAS have a distinct plasma protein profile compared with controls. STUDY DESIGN: We obtained plasma samples prior to delivery from 16 participants with PAS and 10 controls with similar gestational ages (35.1 weeks versus 35.5 weeks respectively). We analyzed plasma samples by SOMAscan®, an aptamer-based proteomics platform, for alterations in 1,305 unique proteins. Heat maps of the most differentially-expressed proteins (T test p<0.01) were generated with Morpheus (Broad Institute, Cambridge, MA). Principal component analysis was performed using all 1,305 proteins and the top 21 dysregulated proteins. We then confirmed dysregulated proteins using enzyme-linked immunosorbent assay (ELISA) and report significant differences between PAS and controls (Wilcoxon-rank sum test p<0.05). RESULTS: Many of the top 50 proteins significantly dysregulated in participants with PAS were inflammatory cytokines, factors regulating vascular remodeling, and extracellular matrix proteins regulating invasion. PCA using the top 21 proteins distinctly separated the PAS cases from controls (P <0.01). Using ELISA, we confirmed 4 proteins that were dysregulated in PAS compared with controls: Median antithrombin III concentrations (240.4 mg/ml vs 150.3 mg/ml, P=0.002), median plasminogen activator inhibitor 1 concentrations (4.1ng/ml vs 7.1 ng/ml, P <0.001), soluble Tie2 (13.5 ng/ml vs 10.4 ng/ml, P=0.02), soluble VEGF receptor 2 (9.0 ng/ml vs 5.9 ng/ml, P=0.003). CONCLUSION: Participants with PAS had a unique and distinct plasma protein signature.
INTRODUCTION: Many cases of placenta accreta spectrum (PAS) are not diagnosed antenatally, despite identified risk factors and improved imaging methods. Identification of plasma protein biomarkers could further improve antenatal diagnosis of PAS. OBJECTIVE: The purpose of this study was to determine if women with PAS have a distinct plasma protein profile compared with controls. STUDY DESIGN: We obtained plasma samples prior to delivery from 16 participants with PAS and 10 controls with similar gestational ages (35.1 weeks versus 35.5 weeks respectively). We analyzed plasma samples by SOMAscan®, an aptamer-based proteomics platform, for alterations in 1,305 unique proteins. Heat maps of the most differentially-expressed proteins (T test p<0.01) were generated with Morpheus (Broad Institute, Cambridge, MA). Principal component analysis was performed using all 1,305 proteins and the top 21 dysregulated proteins. We then confirmed dysregulated proteins using enzyme-linked immunosorbent assay (ELISA) and report significant differences between PAS and controls (Wilcoxon-rank sum test p<0.05). RESULTS: Many of the top 50 proteins significantly dysregulated in participants with PAS were inflammatory cytokines, factors regulating vascular remodeling, and extracellular matrix proteins regulating invasion. PCA using the top 21 proteins distinctly separated the PAS cases from controls (P <0.01). Using ELISA, we confirmed 4 proteins that were dysregulated in PAS compared with controls: Median antithrombin III concentrations (240.4 mg/ml vs 150.3 mg/ml, P=0.002), median plasminogen activator inhibitor 1 concentrations (4.1ng/ml vs 7.1 ng/ml, P <0.001), soluble Tie2 (13.5 ng/ml vs 10.4 ng/ml, P=0.02), soluble VEGF receptor 2 (9.0 ng/ml vs 5.9 ng/ml, P=0.003). CONCLUSION:Participants with PAS had a unique and distinct plasma protein signature.
Authors: William Yakah; Pratibha Singh; Joanne Brown; Barbara Stoll; Doug Burrin; Muralidhar H Premkumar; Hasan H Otu; Xuesong Gu; Simon T Dillon; Towia A Libermann; Steven D Freedman; Camilia R Martin Journal: Am J Physiol Gastrointest Liver Physiol Date: 2020-11-25 Impact factor: 4.052