Proteomic identification of biomarkers in maternal plasma that predict the outcome of rescue cerclage for cervical insufficiency
OBJECTIVE: We sought to identify plasma protein biomarkers that are predictive of the outcome of rescue cerclage in patients with cervical insufficiency.
METHODS: This retrospective cohort study included 39 singleton pregnant women undergoing rescue cerclage for cervical insufficiency (17-25 weeks) who gave plasma samples. Three sets of pooled plasma samples from controls (cerclage success, n = 10) and cases (cerclage failure, n = 10, defined as spontaneous preterm delivery at <33 weeks) were labeled with 6-plex tandem mass tag (TMT) reagents and analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed proteins between the two groups were selected from the TMT-based quantitative analysis. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was further used to verify the candidate proteins of interest in patients with cervical insufficiency in the final cohort (n = 39).
RESULTS: From MRM-MS analysis of the 40 proteins showing statistically significant changes (P < 0.05) from the TMT-based quantitative analysis, plasma IGFBP-2, PSG4, and PGLYRP2 levels were found to be significantly increased, whereas plasma MET and LXN levels were significantly decreased in women with cerclage failure. Of these, IGFBP-2, PSG4, and LXN levels in plasma were independent of cervical dilatation. A multiple-biomarker panel was developed for the prediction of cerclage failure, using a stepwise regression procedure, which included the plasma IGFBP-2, PSG4, and LXN (area under the curve [AUC] = 0.916). The AUC for this multiple-biomarker panel was significantly greater than the AUC for any single biomarker included in the multi-biomarker model.
CONCLUSIONS: Proteomic analysis identified useful and independent plasma biomarkers (IGFBP-2, PSG4, and LXN; verified by MRM) that predict poor pregnancy outcome following rescue cerclage. Their combined analysis in a multi-biomarker panel significantly improved predictability.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
PloS one - 16(2021), 4 vom: 15., Seite e0250031 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dan, Kisoon [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.09.2021 Date Revised 24.09.2021 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0250031 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324120206 |
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| 041 | |a eng | ||
| 100 | 1 | |a Dan, Kisoon |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Proteomic identification of biomarkers in maternal plasma that predict the outcome of rescue cerclage for cervical insufficiency |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 24.09.2021 | ||
| 500 | |a Date Revised 24.09.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: We sought to identify plasma protein biomarkers that are predictive of the outcome of rescue cerclage in patients with cervical insufficiency | ||
| 520 | |a METHODS: This retrospective cohort study included 39 singleton pregnant women undergoing rescue cerclage for cervical insufficiency (17-25 weeks) who gave plasma samples. Three sets of pooled plasma samples from controls (cerclage success, n = 10) and cases (cerclage failure, n = 10, defined as spontaneous preterm delivery at <33 weeks) were labeled with 6-plex tandem mass tag (TMT) reagents and analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed proteins between the two groups were selected from the TMT-based quantitative analysis. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was further used to verify the candidate proteins of interest in patients with cervical insufficiency in the final cohort (n = 39) | ||
| 520 | |a RESULTS: From MRM-MS analysis of the 40 proteins showing statistically significant changes (P < 0.05) from the TMT-based quantitative analysis, plasma IGFBP-2, PSG4, and PGLYRP2 levels were found to be significantly increased, whereas plasma MET and LXN levels were significantly decreased in women with cerclage failure. Of these, IGFBP-2, PSG4, and LXN levels in plasma were independent of cervical dilatation. A multiple-biomarker panel was developed for the prediction of cerclage failure, using a stepwise regression procedure, which included the plasma IGFBP-2, PSG4, and LXN (area under the curve [AUC] = 0.916). The AUC for this multiple-biomarker panel was significantly greater than the AUC for any single biomarker included in the multi-biomarker model | ||
| 520 | |a CONCLUSIONS: Proteomic analysis identified useful and independent plasma biomarkers (IGFBP-2, PSG4, and LXN; verified by MRM) that predict poor pregnancy outcome following rescue cerclage. Their combined analysis in a multi-biomarker panel significantly improved predictability | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Lxn protein, human |2 NLM | |
| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
| 650 | 7 | |a PSG4 protein, human |2 NLM | |
| 650 | 7 | |a Pregnancy-Specific beta 1-Glycoproteins |2 NLM | |
| 650 | 7 | |a peptidoglycan recognition protein |2 NLM | |
| 650 | 7 | |a Insulin-Like Growth Factor II |2 NLM | |
| 650 | 7 | |a 67763-97-7 |2 NLM | |
| 650 | 7 | |a MET protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-met |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Lee, Ji Eun |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Dohyun |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Sun Min |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Subeen |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hyeon Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Kyo Hoon |e verfasserin |4 aut | |
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