Department of Obstetrics and Gynecology, University Hospital Basel, Basel, Switzerland.
Fetal Diagn Ther. 2012;31(3):147-53. doi: 10.1159/000337325. Epub 2012 Mar 29.
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.
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.
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.
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.
我们的目的是在同质人群中鉴定出可用于预测子痫前期的新的生物标志物候选物。在这项研究中，我们在基因组水平上筛选了来自严重子痫前期患者的胎盘绒毛组织中的基因表达情况，并与正常健康妊娠进行了比较。
在计划性剖宫产术后，从 9 例子痫前期患者和 7 例正常血压对照组的胎盘绒毛组织中提取总 RNA。在样本混合后，使用 6 个 Affymetrix Human Gene 1.0 ST 芯片进行基因表达分析，随后进行定量 RT-PCR，并在患者的血清中对选定的标志物进行蛋白质水平验证。
共鉴定出 896 个显著差异表达的基因（p ≤ 0.05）。将这些基因限制在存在于循环中的分子后，选择了 9 个上调和 5 个下调的基因。其中 4 个（β-hCG、HTRA4、LHB1 均上调；NOX4 下调）通过定量实时 RT-PCR 得到验证。最后，通过母体血浆蛋白水平分析，证实了其中 2 个基因（LHB 和 β-hCG）在子痫前期病例和对照组之间存在显著差异。
我们鉴定出 14 个子痫前期的潜在新生物标志物候选物，并通过定量 RT-PCR 验证了其中 4 个，随后通过血清蛋白分析验证了其中 2 个。进一步的研究将评估最佳的标志物组合，以实现对子痫前期的即时预测。
