Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia

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http://hdl.handle.net/10138/160418

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van Uitert , M , Moerland , P D , Enquobahrie , D A , Laivuori , H , van der Post , J A M , Ris-Stalpers , C & Afink , G B 2015 , ' Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia ' , PLoS One , vol. 10 , no. 7 , 0132468 . https://doi.org/10.1371/journal.pone.0132468

Title: Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia
Author: van Uitert, Miranda; Moerland, Perry D.; Enquobahrie, Daniel A.; Laivuori, Hannele; van der Post, Joris A. M.; Ris-Stalpers, Carrie; Afink, Gijs B.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2015-07-14
Language: eng
Number of pages: 15
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/160418
Abstract: Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.
Subject: RUBINSTEIN-TAYBI-SYNDROME
GENE-EXPRESSION
MICROARRAY ANALYSIS
PREGNANCIES
HYPOXIA
GROWTH
EP300
UPDATE
PATHOGENESIS
RECRUITMENT
3111 Biomedicine
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