差异基因 GO分析

Analysis of differentially expressed genes in placental tissues of preeclampsia patients using microarray combined with

the Connectivity Map database

Y.Song a,J.Liu a,*,S.Huang a,L.Zhang b

a Department of Obstetrics&Gynecology,Peking Union Medical College Hospital,Chinese Academy of Medical Science,Peking Union Medical College, Beijing,PR China

b BioChain(Beijing)Science&Technology Inc.,No.7A,Yongchang North Rd,Business Development Area,Beijing,PR China

a r t i c l e i n f o

Article history:

Accepted19September2013

Keywords:

Preeclampsia

Microarray

Expression profiles Connectivity Map database a b s t r a c t

Preeclampsia(PE),which affects2e7%of human pregnancies,causes significant maternal and neonatal morbidity and mortality.To better understand the pathophysiology of PE,the gene expression profiles of placental tissue from5controls and5PE patients were assessed using microarray.A total of224tran-scripts were significantly differentially expressed(>2-fold change and q value<0.05,SAM software). Gene Ontology(GO)enrichment analysis indicated that genes involved in hypoxia and oxidative and reductive processes were significantly changed.Three differentially expressed genes(DEGs)involved in these biological processes were further verified by quantitative real-time PCR.Finally,the potential therapeutic agents for PE were explored via the Connectivity Map database.In conclusion,the data obtained in this study might provide clues to better understand the pathophysiology of PE and to identify potential therapeutic agents for PE patients.

Ó2013Elsevier Ltd.All rights reserved.

1.Introduction

One of the leading causes of mortality and morbidity amongst pregnant women and their offspring is PE,which affects2e7%of all pregnancies,depending on the diagnostic criteria and the patients’ethnicity[1].PE is generally defined as new hyperten-sion and substantial proteinuria at or after20weeks gestation.It is generally accepted that PE involves two pathophysiological stages.Thefirst stage occurs when impaired trophoblasts invade the myometrial arteries,leading to reduced uteroplacental arte-rialflow and episodes of irregular placental perfusion,followed by ischemic hypoxia and oxidative stress.The second stage of PE is thought to be the maternal response to abnormal placentation. An intrinsic failure in trophoblast differentiation at different time points of ontogeny may lead to either a mild disorder with late-onset appearance or to intrauterine growth retardation,poten-tially complicated with maternal symptoms[2].Systemic endothelial dysfunction appears to be an important common factor[3,4].

Despite breakthroughs in the understanding of the patho-genesis of PE,the mechanisms that ultimately trigger the disease are still not clearly elucidated[5].It seems clear that the development of PE requires the placenta,given that PE can occur in molar pregnancies wherein a placenta,but no fetus,is present.Furthermore,the only effective treatment of PE is de-livery of the placenta[6,7].Previous studies also showed that PE has a strong familial predisposition,and it has been concluded that a hereditary element may exist.Therefore,it is clinically useful to compare the gene expression profiles of placentas with and without PE to better understand the pathophysiology of this disease and to aid in the development of new therapies [8,9].

Microarray technology is a powerful tool for simultaneously assessing the expression of a high number of genes and to pinpoint the patterns of gene expression associated with a disease[10].To date,a number of microarray studies have been conducted on the global gene expression profiles of the PE placenta,and several important genes have been identified using this strategy[11e18]. However,a comparison of different studies performed using DNA microarrays has shown poor overlap,and therefore,only a minority of DEGs are shared between these studies.The resulting differences may be due to the diverse genetic backgrounds of the study pop-ulation,the use of different platforms and protocols,and the impact of individual differences on expression signatures[16].Therefore, to better understand the events leading to PE,it is necessary to

*Corresponding author.

E-mail address:juntao_liu@(J.

Liu).Contents lists available at ScienceDirect

Placenta

journal homepage:www.elsev /locat e/placen

ta

0143-4004/$e see front matterÓ2013Elsevier Ltd.All rights reserved.

/10.1016/j.placenta.2013.09.013

Placenta34(2013)1190e1195