{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:12:58Z","timestamp":1792289578030,"version":"4.4.0"},"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["2020R1F1A1048362"],"award-info":[{"award-number":["2020R1F1A1048362"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This was a retrospective cohort study comprising 104 singleton pregnant women with PTL (24\u201332 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Ninety-one proteins were differentially expressed (<jats:italic>P<\/jats:italic> &lt; 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 \u2164 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0259265","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T17:38:14Z","timestamp":1635442694000},"page":"e0259265","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection\/inflammation"],"prefix":"10.1371","volume":"16","author":[{"given":"Ji Eun","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3550-9686","authenticated-orcid":true,"given":"Kyo Hoon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Ji","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Mi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Woong","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyong-No","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"issue":"9606","key":"pone.0259265.ref001","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(08)60074-4","article-title":"Epidemiology and causes of preterm birth","volume":"371","author":"RL Goldenberg","year":"2008","journal-title":"Lancet"},{"issue":"2","key":"pone.0259265.ref002","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.siny.2015.12.011","article-title":"The epidemiology, etiology, and costs of preterm birth.","volume":"21","author":"HA Frey","year":"2016","journal-title":"Semin Fetal Neonatal Med"},{"issue":"1","key":"pone.0259265.ref003","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ajog.2016.01.004","article-title":"Preterm neonatal morbidity and mortality by gestational age: a contemporary cohort.","volume":"215","author":"TA Manuck","year":"2016","journal-title":"Am J Obstet Gynecol"},{"issue":"6198","key":"pone.0259265.ref004","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.1251816","article-title":"Preterm labor: one syndrome, many causes","volume":"345","author":"R Romero","year":"2014","journal-title":"Science"},{"issue":"6","key":"pone.0259265.ref005","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1080\/00016340802005126","article-title":"Spontaneous preterm birth, a clinical dilemma: etiologic, pathophysiologic and genetic heterogeneities and racial disparity.","volume":"87","author":"R. 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