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Extracellular vesicles yield predictive pre-eclampsia biomarkers

Circulating extracellular vesicles (EVs) such as cholera toxin B chain (CTB)- or annexin V (AV)-binding EVs were previously shown to be rich sources of biomarkers. Here we test if previously identified pre-eclampsia (PE) candidate biomarkers, TIMP-1 in CTB-EVs (CTB-TIMP) and PAI-1 in AV-EVs (AV-PAI)...

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Autores principales: Tan, Kok Hian, Tan, Soon Sim, Ng, Mor Jack, Tey, Wan Shi, Sim, Wei Kian, Allen, John Carson, Lim, Sai Kiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738645/
https://www.ncbi.nlm.nih.gov/pubmed/29296254
http://dx.doi.org/10.1080/20013078.2017.1408390
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author Tan, Kok Hian
Tan, Soon Sim
Ng, Mor Jack
Tey, Wan Shi
Sim, Wei Kian
Allen, John Carson
Lim, Sai Kiang
author_facet Tan, Kok Hian
Tan, Soon Sim
Ng, Mor Jack
Tey, Wan Shi
Sim, Wei Kian
Allen, John Carson
Lim, Sai Kiang
author_sort Tan, Kok Hian
collection PubMed
description Circulating extracellular vesicles (EVs) such as cholera toxin B chain (CTB)- or annexin V (AV)-binding EVs were previously shown to be rich sources of biomarkers. Here we test if previously identified pre-eclampsia (PE) candidate biomarkers, TIMP-1 in CTB-EVs (CTB-TIMP) and PAI-1 in AV-EVs (AV-PAI) complement plasma PlGF in predicting PE in a low-risk obstetric population. Eight hundred and forty-three prospectively banked plasma samples collected at 28 + 0 to 32 + 0 gestation weeks in the Neonatal and Obstetrics Risk Assessment (NORA) cohort study were assayed by sandwich ELISAs for plasma PlGF, CTB-TIMP1 and AV-PAI1. Nineteen patients subsequently developed PE 7.3 (±2.9) weeks later at a mean gestational age of 36.1 ± 3.5 weeks. The biomarkers were assessed for their predictive accuracy for PE using stepwise multivariate logistic regression analysis with Firth correction and Areas under the curve (AUC). To achieve 100% sensitivity in predicting PE, the cut-off for plasma PlGF, CTB-TIMP1 & AV-PAI1 were set at <1235, ≤300 or >1300 and <10,550 pg/mL plasma, respectively. The corresponding AUCs, specificity and PPV at a 95% confidence interval were 0.92, 52.1% and 4.7%; 0.72, 44.5% and 4.0%; and 0.69, 21.5% and 2.9%, respectively. At 100% sensitivity, the three biomarkers had a combined AUC of 0.96, specificity of 78.6%, and PPV of 9.9%. This is the first large cohort validation of the utility of EV-associated analytes as disease biomarkers. Specifically, EV biomarkers enhanced the predictive robustness of an existing PE biomarker sufficiently to justify PE screening in a low-risk general obstetric population.
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spelling pubmed-57386452018-01-02 Extracellular vesicles yield predictive pre-eclampsia biomarkers Tan, Kok Hian Tan, Soon Sim Ng, Mor Jack Tey, Wan Shi Sim, Wei Kian Allen, John Carson Lim, Sai Kiang J Extracell Vesicles Research Article Circulating extracellular vesicles (EVs) such as cholera toxin B chain (CTB)- or annexin V (AV)-binding EVs were previously shown to be rich sources of biomarkers. Here we test if previously identified pre-eclampsia (PE) candidate biomarkers, TIMP-1 in CTB-EVs (CTB-TIMP) and PAI-1 in AV-EVs (AV-PAI) complement plasma PlGF in predicting PE in a low-risk obstetric population. Eight hundred and forty-three prospectively banked plasma samples collected at 28 + 0 to 32 + 0 gestation weeks in the Neonatal and Obstetrics Risk Assessment (NORA) cohort study were assayed by sandwich ELISAs for plasma PlGF, CTB-TIMP1 and AV-PAI1. Nineteen patients subsequently developed PE 7.3 (±2.9) weeks later at a mean gestational age of 36.1 ± 3.5 weeks. The biomarkers were assessed for their predictive accuracy for PE using stepwise multivariate logistic regression analysis with Firth correction and Areas under the curve (AUC). To achieve 100% sensitivity in predicting PE, the cut-off for plasma PlGF, CTB-TIMP1 & AV-PAI1 were set at <1235, ≤300 or >1300 and <10,550 pg/mL plasma, respectively. The corresponding AUCs, specificity and PPV at a 95% confidence interval were 0.92, 52.1% and 4.7%; 0.72, 44.5% and 4.0%; and 0.69, 21.5% and 2.9%, respectively. At 100% sensitivity, the three biomarkers had a combined AUC of 0.96, specificity of 78.6%, and PPV of 9.9%. This is the first large cohort validation of the utility of EV-associated analytes as disease biomarkers. Specifically, EV biomarkers enhanced the predictive robustness of an existing PE biomarker sufficiently to justify PE screening in a low-risk general obstetric population. Taylor & Francis 2017-12-13 /pmc/articles/PMC5738645/ /pubmed/29296254 http://dx.doi.org/10.1080/20013078.2017.1408390 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tan, Kok Hian
Tan, Soon Sim
Ng, Mor Jack
Tey, Wan Shi
Sim, Wei Kian
Allen, John Carson
Lim, Sai Kiang
Extracellular vesicles yield predictive pre-eclampsia biomarkers
title Extracellular vesicles yield predictive pre-eclampsia biomarkers
title_full Extracellular vesicles yield predictive pre-eclampsia biomarkers
title_fullStr Extracellular vesicles yield predictive pre-eclampsia biomarkers
title_full_unstemmed Extracellular vesicles yield predictive pre-eclampsia biomarkers
title_short Extracellular vesicles yield predictive pre-eclampsia biomarkers
title_sort extracellular vesicles yield predictive pre-eclampsia biomarkers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738645/
https://www.ncbi.nlm.nih.gov/pubmed/29296254
http://dx.doi.org/10.1080/20013078.2017.1408390
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