Microarray Screening for Novel Preeclampsia Biomarker Candidates

Abstract

Introduction: Our aim was to identify novel biomarker candidates for the near-term prediction of preeclampsia in a homogenous collective. In this study, we screened at the genome-wide level for gene expression in placental villous tissue from patients with severe preeclampsia in comparison to normal healthy pregnancies. Material and Methods: Total RNA was extracted from placental villous tissue from 9 preeclamptic patients and 7 normotensive controls after scheduled cesarean sections. After sample pooling, gene expression analysis was performed using six Affymetrix Human Gene 1.0 ST arrays, followed by quantitative RT-PCR and validation of selected markers in the serum of patients at the protein level. Results: In total, 896 significantly differentially expressed genes were identified (p ≤ 0.05). After restricting these to molecules present in the circulation, 9 upregulated and 5 downregulated genes were selected. Four of them (β-hCG, HTRA4, LHB1, all upregulated; and NOX4, downregulated) were validated by quantitative real-time RT-PCR. Finally, the maternal plasma protein levels of 2 of these genes (LHB and β-hCG) were confirmed to be significantly different between preeclampsia cases and controls. Discussion: We identified 14 potential new biomarker candidates for preeclampsia and validated 4 of them by quantitative RT-PCR and 2 of them with subsequent serum protein analyses. Further studies will assess the optimal marker combination for the imminent prediction of impending preeclampsia.

The Impact of Maternal-Fetal Genetic Conflict Situations on the Pathogenesis of Preeclampsia

“…Higher methylation was also observed in some genes in the preeclampsia (Jia et al 2012). Here, we showed that the differentially expressed genes in preeclampsia placental tissues were mainly enriched in several pathways associated with pregnancy maintenance, metabolism, oxidative stress and oxidative metabolism, cell cycle regulation, embryogenesis and development, implantation, placentation and decidualization, immune modulation, and vascular function (Zhou et al 2006;Laivuori 2007;Founds et al 2009;Johansson et al 2011;Løset et al 2011;Rajakumar et al 2011;Sado et al 2011;Tsai et al 2011;Jia et al 2012;Lapaire et al 2012). We summarized the major functional categories on the differential gene expression profile between preeclampsia and normal placentas ( Table 1).…”

“…This review provides a detailed overview of typical genome-wide studies that have been conducted so far on preeclamptic placental tissue samples (Zhou et al 2006;Laivuori 2007;Founds et al 2009;Johansson et al 2011;Løset et al 2011;Rajakumar et al 2011;Sado et al 2011;Tsai et al 2011;Jia et al 2012;Lapaire et al 2012).…”

“…A number of preeclampsia susceptibility genes were identified (Laivuori 2007;Kang et al 2011;Løset et al 2011;Rajakumar et al 2011;Lapaire et al 2012). Higher methylation was also observed in some genes in the preeclampsia (Jia et al 2012).…”

Partial least squares-based gene expression analysis in preeclampsia

“…Several gene expression studies (Lapaire et al, 2012;Louwen et al, 2012;Meng et al, 2012;Zhou et al, 2013) have been conducted to investigate expression differences between preeclampsia patients and healthy controls. The major challenge for microarray analysis is to develop a suitable statistical model to deal with the small sample number and large number of genes.…”

Predictive Value of Free β-hCG Multiple of the Median for Women with Preeclampsia

“…Previous evidence has shown that weight and smoking status are risk factors for the pathogenesis of PE [5]. Recently, there has been increasing evidence that free β-human chorionic gonadotropin (β-hCG) is associated with PE [6]. …”