Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.
Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.
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DOI：
10.1371/journal.pone.0116508
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Cox BJ
中科院分区：
文献类型：
--
作者：
Leavey K;Bainbridge SA;Cox BJ
先兆子痫 (PE) 是一种危及生命的妊娠期高血压病症，影响所有妊娠的 3-5%。迄今为止，PE 尚无治愈方法、早期检测标志物或有效治疗方法，除非切除被认为是致病器官的胎盘，否则可能导致早产。此外，许多试图鉴定“PE特异性”基因的小型胎盘微阵列研究也得出了不一致的结果。因此，我们假设先兆子痫是一种多因素疾病，涵盖多个病理学亚类，并且大队列胎盘基因表达分析将揭示这些亚类。为了验证我们的假设，我们利用已知的生物信息学方法跨多个平台聚合 7 个微阵列数据集，以生成包含 173 个患者样本的大型数据集，其中包括 77 个先兆子痫患者样本。这些患者样本的无监督聚类揭示了 PE 的三个不同的分子亚类。其中包括一个“典型”PE亚类，该亚类显示已知PE标记物和与氧合作用不良和分泌增加相关的基因表达升高，以及其他两个亚类，可能代表母体对妊娠的不良反应和先兆子痫的免疫学表现。我们的分析为PE患者的异质性提供了新的线索，并为未来的研究提供了额外的途径。希望我们基于分子多样性对先兆子痫的细分最终能够开发出针对这种疾病的稳健诊断和基于患者的治疗方法。
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. 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. 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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