发现和验证细胞外 miRNA 生物标志物用于无症状孕妇子痫前期的无创预测。
Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women.
机构信息
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
These authors contributed equally.
出版信息
Cell Rep Med. 2020 May 19;1(2). doi: 10.1016/j.xcrm.2020.100013.
Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.
开发有效的子痫前期预防和治疗策略受到缺乏识别高危妊娠的准确方法的限制。我们对母体血清细胞外 RNA（exRNA）进行小 RNA 测序（RNA-seq），以发现和验证在以后发生子痫前期的患者中差异表达的 microRNAs（miRNAs）。在 17 至 28 周妊娠龄（GA）时，从 73 例子痫前期病例和 139 例对照中采集血清，分为单独的发现和验证队列，通过小 RNA-seq 进行分析。单变量和双变量 miRNA 生物标志物的发现和验证表明，双变量生物标志物的验证率明显高于单变量生物标志物。大多数经过验证的生物标志物包含 miR-155-5p，据报道，它通过肿瘤坏死因子α（TNF-α）介导子痫前期相关的内皮型一氧化氮合酶（eNOS）抑制。去卷积分析表明，几个经过验证的 miRNA 生物标志物来自胎盘，并且可能由胎盘特异性细胞外囊泡携带。
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