Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation

<h4>Objective</h4> We sought to identify plasma biomarkers associated with spontaneous preterm birth (SPTB, delivery within 21 days of sampling) in women with preterm labor (PTL) without intra-amniotic infection/inflammation (IAI) using label-free quantitative proteomic analysis, as well...

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Autores principales: Ji Eun Lee, Kyo Hoon Park, Hyeon Ji Kim, Yu Mi Kim, Ji-Woong Choi, Sue Shin, Kyong-No Lee
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spelling oai:doaj.org-article:a33dc2a2e91b4904a4f5a503a94b87fb2021-11-04T06:49:36ZProteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation1932-6203https://doaj.org/article/a33dc2a2e91b4904a4f5a503a94b87fb2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553083/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4> We sought to identify plasma biomarkers associated with spontaneous preterm birth (SPTB, delivery within 21 days of sampling) in women with preterm labor (PTL) without intra-amniotic infection/inflammation (IAI) using label-free quantitative proteomic analysis, as well as to elucidate specific protein pathways involved in these cases. <h4>Methods</h4> This was a retrospective cohort study comprising 104 singleton pregnant women with PTL (24–32 weeks) who underwent amniocentesis and demonstrated no evidence of IAI. Analysis of pooled plasma samples collected from SPTB cases and term birth (TB) controls (n = 10 for each group) was performed using label-free quantitative mass spectrometry for proteome profiling in a nested case-control study design. Eight candidate proteins of interest were validated by ELISA-based assay and a clot-based assay in the total cohort. <h4>Results</h4> Ninety-one proteins were differentially expressed (P < 0.05) in plasma samples obtained from SPTB cases, of which 53 (58.2%) were upregulated and 38 (41.8%) were downregulated when compared to TD controls. A validation study confirmed that plasma from women who delivered spontaneously within 21 days of sampling contained significantly higher levels of coagulation factor Ⅴ and lower levels of S100 calcium binding protein A9 (S100A9), especially the former which was independent of baseline variables. The top-ranked pathways related to the 91 differentially expressed proteins were liver-X-receptor/retinoid X receptor (RXR) activation, acute phase response signaling, farnesoid X receptor/RXR activation, coagulation system, and complement system. <h4>Conclusions</h4> Proteomic analyses in this study identified potential novel biomarkers (i.e., coagulation factor V and S100A9) and potential protein pathways in plasma associated with SPTB in the absence of IAI in women with PTL. The present findings provide novel insights into the molecular pathogenesis and therapeutic targets specific for idiopathic SPTB.Ji Eun LeeKyo Hoon ParkHyeon Ji KimYu Mi KimJi-Woong ChoiSue ShinKyong-No LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ji Eun Lee
Kyo Hoon Park
Hyeon Ji Kim
Yu Mi Kim
Ji-Woong Choi
Sue Shin
Kyong-No Lee
Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation
description <h4>Objective</h4> We sought to identify plasma biomarkers associated with spontaneous preterm birth (SPTB, delivery within 21 days of sampling) in women with preterm labor (PTL) without intra-amniotic infection/inflammation (IAI) using label-free quantitative proteomic analysis, as well as to elucidate specific protein pathways involved in these cases. <h4>Methods</h4> This was a retrospective cohort study comprising 104 singleton pregnant women with PTL (24–32 weeks) who underwent amniocentesis and demonstrated no evidence of IAI. Analysis of pooled plasma samples collected from SPTB cases and term birth (TB) controls (n = 10 for each group) was performed using label-free quantitative mass spectrometry for proteome profiling in a nested case-control study design. Eight candidate proteins of interest were validated by ELISA-based assay and a clot-based assay in the total cohort. <h4>Results</h4> Ninety-one proteins were differentially expressed (P < 0.05) in plasma samples obtained from SPTB cases, of which 53 (58.2%) were upregulated and 38 (41.8%) were downregulated when compared to TD controls. A validation study confirmed that plasma from women who delivered spontaneously within 21 days of sampling contained significantly higher levels of coagulation factor Ⅴ and lower levels of S100 calcium binding protein A9 (S100A9), especially the former which was independent of baseline variables. The top-ranked pathways related to the 91 differentially expressed proteins were liver-X-receptor/retinoid X receptor (RXR) activation, acute phase response signaling, farnesoid X receptor/RXR activation, coagulation system, and complement system. <h4>Conclusions</h4> Proteomic analyses in this study identified potential novel biomarkers (i.e., coagulation factor V and S100A9) and potential protein pathways in plasma associated with SPTB in the absence of IAI in women with PTL. The present findings provide novel insights into the molecular pathogenesis and therapeutic targets specific for idiopathic SPTB.
format article
author Ji Eun Lee
Kyo Hoon Park
Hyeon Ji Kim
Yu Mi Kim
Ji-Woong Choi
Sue Shin
Kyong-No Lee
author_facet Ji Eun Lee
Kyo Hoon Park
Hyeon Ji Kim
Yu Mi Kim
Ji-Woong Choi
Sue Shin
Kyong-No Lee
author_sort Ji Eun Lee
title Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation
title_short Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation
title_full Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation
title_fullStr Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation
title_full_unstemmed Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation
title_sort proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/a33dc2a2e91b4904a4f5a503a94b87fb
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