Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation
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 prote...
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| creator | Lee, Ji Eun Park, Kyo Hoon Kim, Hyeon Ji Kim, Yu Mi Choi, Ji-Woong Shin, Sue Lee, Kyong-No |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1371/journal.pone.0259265 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0259265</identifier><identifier>PMID: 34710180</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Amniocentesis ; Biology and Life Sciences ; Biomarkers ; Biomarkers - blood ; Birth ; Calcium-binding protein ; Calgranulin B - blood ; Childbirth & labor ; Coagulation ; Coagulation factors ; Complement activation ; Enzyme-linked immunosorbent assay ; Factor V ; Factor V - analysis ; Female ; Gynecology ; Health aspects ; Hospitals ; Humans ; Independent variables ; Infections ; Inflammation ; Labor ; Laboratories ; Liver X receptors ; Mass spectrometry ; Mass spectroscopy ; Medical schools ; Medicine ; Medicine and Health Sciences ; Methods ; Obstetrics ; Pathogenesis ; Physiological aspects ; Plasma ; Pregnant women ; Premature birth ; Premature Birth - blood ; Premature labor ; Proteins ; Proteome - chemistry ; Proteomes ; Proteomics ; Receptors ; Retinoid X receptors ; Risk factors ; Sampling ; Therapeutic targets ; Womens health</subject><ispartof>PloS one, 2021-10, Vol.16 (10), p.e0259265-e0259265</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Lee et al 2021 Lee et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c653t-f146dc305645b73479be96297177c2a551e27afe4759761f4163328ebfc463943</citedby><cites>FETCH-LOGICAL-c653t-f146dc305645b73479be96297177c2a551e27afe4759761f4163328ebfc463943</cites><orcidid>0000-0003-3550-9686</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553083/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553083/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34710180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Ji Eun</creatorcontrib><creatorcontrib>Park, Kyo Hoon</creatorcontrib><creatorcontrib>Kim, Hyeon Ji</creatorcontrib><creatorcontrib>Kim, Yu Mi</creatorcontrib><creatorcontrib>Choi, Ji-Woong</creatorcontrib><creatorcontrib>Shin, Sue</creatorcontrib><creatorcontrib>Lee, Kyong-No</creatorcontrib><title>Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.
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.</description><subject>Adult</subject><subject>Amniocentesis</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Birth</subject><subject>Calcium-binding protein</subject><subject>Calgranulin B - blood</subject><subject>Childbirth & labor</subject><subject>Coagulation</subject><subject>Coagulation factors</subject><subject>Complement activation</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Factor V</subject><subject>Factor V - analysis</subject><subject>Female</subject><subject>Gynecology</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Independent variables</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Labor</subject><subject>Laboratories</subject><subject>Liver X receptors</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Obstetrics</subject><subject>Pathogenesis</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Pregnant women</subject><subject>Premature birth</subject><subject>Premature Birth - blood</subject><subject>Premature labor</subject><subject>Proteins</subject><subject>Proteome - chemistry</subject><subject>Proteomes</subject><subject>Proteomics</subject><subject>Receptors</subject><subject>Retinoid X receptors</subject><subject>Risk factors</subject><subject>Sampling</subject><subject>Therapeutic targets</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9uO0zAQhiMEYpfCGyCIhITgol07ju3kBmm14lBppUWcbq2JO2m9OHGxnV14Ex4Xt01XLeKCK1ueb_7x_PZk2VNKZpRJenbtBt-Dna1djzNS8LoQ_F52SmtWTEVB2P2D_Un2KIRrQjirhHiYnbBSUkIrcpr9_uhdRNcZnZsF9tG0RkM0rs9dm_fuBm2-thA6yBvjOvDf0YccQnDaQMRFfmviKg_pDhF6dEPI1x4j-i7hPkVMn9-6Dvsdt49ZaJzfHrkhJqZFvSl5lnYWum5b_3H2oAUb8Mm4TrKv795-ufgwvbx6P784v5xqwVmctrQUC80IFyVvZOqrbrAWRS2plLoAzikWElosJa-loG1JBWNFhU2rS8Hqkk2y5zvdtXVBjaYGVfBKSsLLmiRiviMWDq7V2ptkwy_lwKjtgfNLBT4abVEBY4tUtcCaNim1hLLlwAmDumwq2TZJ681YbWg6XOjkuAd7JHoc6c1KLd2NqjhnpGJJ4NUo4N2PAUNUnQkard3Zn-5dE1JVlPGEvvgL_Xd3I7WE1EB6AZfq6o2oOhcV4VSSpDbJXh9ROj04_oxLGEJQ88-f_p-9-nbMvjxgVwg2roKzw-YHhGOw3IHauxA8tneeUaI287BvTm3mQY3zkNKeHfp9l7QfAPYHB_oJFQ</recordid><startdate>20211028</startdate><enddate>20211028</enddate><creator>Lee, Ji Eun</creator><creator>Park, Kyo Hoon</creator><creator>Kim, Hyeon Ji</creator><creator>Kim, Yu Mi</creator><creator>Choi, Ji-Woong</creator><creator>Shin, Sue</creator><creator>Lee, Kyong-No</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3550-9686</orcidid></search><sort><creationdate>20211028</creationdate><title>Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation</title><author>Lee, Ji Eun ; Park, Kyo Hoon ; Kim, Hyeon Ji ; Kim, Yu Mi ; Choi, Ji-Woong ; Shin, Sue ; Lee, Kyong-No</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c653t-f146dc305645b73479be96297177c2a551e27afe4759761f4163328ebfc463943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Amniocentesis</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Birth</topic><topic>Calcium-binding protein</topic><topic>Calgranulin B - blood</topic><topic>Childbirth & labor</topic><topic>Coagulation</topic><topic>Coagulation factors</topic><topic>Complement activation</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Factor V</topic><topic>Factor V - analysis</topic><topic>Female</topic><topic>Gynecology</topic><topic>Health aspects</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Independent variables</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Labor</topic><topic>Laboratories</topic><topic>Liver X receptors</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medical schools</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Methods</topic><topic>Obstetrics</topic><topic>Pathogenesis</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Pregnant women</topic><topic>Premature birth</topic><topic>Premature Birth - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Ji Eun</au><au>Park, Kyo Hoon</au><au>Kim, Hyeon Ji</au><au>Kim, Yu Mi</au><au>Choi, Ji-Woong</au><au>Shin, Sue</au><au>Lee, Kyong-No</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-10-28</date><risdate>2021</risdate><volume>16</volume><issue>10</issue><spage>e0259265</spage><epage>e0259265</epage><pages>e0259265-e0259265</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34710180</pmid><doi>10.1371/journal.pone.0259265</doi><tpages>e0259265</tpages><orcidid>https://orcid.org/0000-0003-3550-9686</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2021-10, Vol.16 (10), p.e0259265-e0259265 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2587705490 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Amniocentesis Biology and Life Sciences Biomarkers Biomarkers - blood Birth Calcium-binding protein Calgranulin B - blood Childbirth & labor Coagulation Coagulation factors Complement activation Enzyme-linked immunosorbent assay Factor V Factor V - analysis Female Gynecology Health aspects Hospitals Humans Independent variables Infections Inflammation Labor Laboratories Liver X receptors Mass spectrometry Mass spectroscopy Medical schools Medicine Medicine and Health Sciences Methods Obstetrics Pathogenesis Physiological aspects Plasma Pregnant women Premature birth Premature Birth - blood Premature labor Proteins Proteome - chemistry Proteomes Proteomics Receptors Retinoid X receptors Risk factors Sampling Therapeutic targets Womens health |
| title | Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T16%3A51%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Proteomic%20identification%20of%20novel%20plasma%20biomarkers%20associated%20with%20spontaneous%20preterm%20birth%20in%20women%20with%20preterm%20labor%20without%20infection/inflammation&rft.jtitle=PloS%20one&rft.au=Lee,%20Ji%20Eun&rft.date=2021-10-28&rft.volume=16&rft.issue=10&rft.spage=e0259265&rft.epage=e0259265&rft.pages=e0259265-e0259265&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0259265&rft_dat=%3Cgale_plos_%3EA680517081%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2587705490&rft_id=info:pmid/34710180&rft_galeid=A680517081&rft_doaj_id=oai_doaj_org_article_a33dc2a2e91b4904a4f5a503a94b87fb&rfr_iscdi=true |