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Proteomic Analysis of Amniotic Fluid Proteins for Predicting the Outcome of Emergency Cerclage in Women with Cervical Insufficiency

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Abstract

We aimed to identify novel biomarkers in amniotic fluid (AF) that predict the outcome of emergency cerclage in women with cervical insufficiency. This retrospective cohort study included 40 singleton pregnant women who received emergency cerclage for cervical insufficiency (17–25 weeks) and underwent amniocentesis. Label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify AF proteins in pooled samples (n = 16) using a nested case-control approach. The six candidate biomarkers of interest were validated by enzyme-linked immunosorbent assays (ELISA) in the final cohort (n = 40). The differentially expressed proteins (DEPs) were analyzed by pathway analysis software. The primary outcome measure was failure of emergency cerclage [defined as spontaneous preterm delivery (SPTD) at < 34 weeks of gestation after cerclage placement]. Sixty-eight proteins were differentially expressed (P < 0.001) in AF from SPTD cases and near-term controls, of which 44 (64.7%) were upregulated and 24 (35.3%) were downregulated. Validation by ELISA confirmed that AF from women with cerclage failure contained significantly higher levels of myeloperoxidase, lactoferrin, glucose-6-phosphate isomerase, lipocalin-2, and lymphocyte cytosolic protein 1, the first four of which were independent of cervical dilatation at presentation. The five pathways with the most differentially regulated proteins were actin cytoskeleton signaling, acute phase response signaling, ILK signaling, glycolysis, and gluconeogenesis. Proteomic analyses of AF in this study identified DEPs and specific protein pathways related to poor prognosis after emergency cerclage for cervical insufficiency. Four novel independent biomarkers in AF for cerclage failure have been identified using proteomics.

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Funding

This study was supported by the Seoul National University Bundang Hospital Research Fund (Grant No. 12–2013-014) and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C0063). The sponsor or funding organization had no role in the design or conduct of this research.

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Author notes

  1. JoonHo Lee and Ji Eun Lee contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea

    JoonHo Lee

  2. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, South Korea

    Ji Eun Lee

  3. Wide River Institute of Immunology, Seoul National University, Hongcheon, South Korea

    Ji-Woong Choi & Mi-Hee Han

  4. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea

    Seung-Yong Seong

  5. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea

    Seung-Yong Seong

  6. Departments of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea

    Kyo Hoon Park & Jeong Woo Park

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  1. JoonHo Lee
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Correspondence to Kyo Hoon Park or Jeong Woo Park.

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ESM 2

The top two interaction networks generated by ingenuity pathway analysis are displayed, respectively, in (A) and (B). Proteins with higher levels of expression in SPTD cases are in red, whereas proteins expressed more in the near-term controls are in green. NF-κB and cytokine are one of the major hubs in each network. Straight lines indicate direct interactions, while dashed lines indicate indirect ones (PNG 729 kb)

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Lee, J., Lee, J.E., Choi, JW. et al. Proteomic Analysis of Amniotic Fluid Proteins for Predicting the Outcome of Emergency Cerclage in Women with Cervical Insufficiency. Reprod. Sci. 27, 1318–1329 (2020). https://doi.org/10.1007/s43032-019-00110-8

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  • DOI: https://doi.org/10.1007/s43032-019-00110-8

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