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Large Scale Aggregate Microarray Analysis Reveals Three Distinct Molecular Subclasses of Human Preeclampsia

BACKGROUND: Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3–5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate...

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Detalles Bibliográficos
Autores principales: Leavey, Katherine, Bainbridge, Shannon A., Cox, Brian J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332506/
https://www.ncbi.nlm.nih.gov/pubmed/25679511
http://dx.doi.org/10.1371/journal.pone.0116508
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author Leavey, Katherine
Bainbridge, Shannon A.
Cox, Brian J.
author_facet Leavey, Katherine
Bainbridge, Shannon A.
Cox, Brian J.
author_sort Leavey, Katherine
collection PubMed
description BACKGROUND: Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3–5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify “PE-specific” genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. RESULTS: To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a “canonical” PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. CONCLUSION: Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.
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spelling pubmed-43325062015-02-24 Large Scale Aggregate Microarray Analysis Reveals Three Distinct Molecular Subclasses of Human Preeclampsia Leavey, Katherine Bainbridge, Shannon A. Cox, Brian J. PLoS One Research Article BACKGROUND: Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3–5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify “PE-specific” genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. RESULTS: To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a “canonical” PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. CONCLUSION: Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder. Public Library of Science 2015-02-13 /pmc/articles/PMC4332506/ /pubmed/25679511 http://dx.doi.org/10.1371/journal.pone.0116508 Text en © 2015 Leavey et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Leavey, Katherine
Bainbridge, Shannon A.
Cox, Brian J.
Large Scale Aggregate Microarray Analysis Reveals Three Distinct Molecular Subclasses of Human Preeclampsia
title Large Scale Aggregate Microarray Analysis Reveals Three Distinct Molecular Subclasses of Human Preeclampsia
title_full Large Scale Aggregate Microarray Analysis Reveals Three Distinct Molecular Subclasses of Human Preeclampsia
title_fullStr Large Scale Aggregate Microarray Analysis Reveals Three Distinct Molecular Subclasses of Human Preeclampsia
title_full_unstemmed Large Scale Aggregate Microarray Analysis Reveals Three Distinct Molecular Subclasses of Human Preeclampsia
title_short Large Scale Aggregate Microarray Analysis Reveals Three Distinct Molecular Subclasses of Human Preeclampsia
title_sort large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332506/
https://www.ncbi.nlm.nih.gov/pubmed/25679511
http://dx.doi.org/10.1371/journal.pone.0116508
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