Urinary Proteomics for Prediction of Preeclampsia
Urinary Proteomics for Prediction of Preeclampsia
复制标题
DOI：
10.1161/hypertensionaha.110.164285
复制
发表时间：
2011-03-01
期刊：
影响因子：
8.3
通讯作者：
Delles, Christian
中科院分区：
文献类型：
--
作者：
Carty, David M.;Siwy, Justyna;Delles, Christian
先兆子痫是胎儿和母亲发病率和死亡率的主要决定因素。我们使用蛋白质组学策略来鉴定在疾病发作前预测先兆子痫的尿生物标志物。我们前瞻性地收集了整个妊娠期妇女的尿液样本。来自随后发生先兆子痫的妇女的妊娠12至16周（n=45）、20周（n=50）和28周（n=18）的样品与对照组（分别为n=86、n=49和n=17）匹配。我们进行了毛细管电泳在线耦合微飞行时间质谱。使用基于支持向量机的软件生成疾病特异性肽模式。通过液相色谱-串联质谱法对候选生物标志物进行测序。通过与非妊娠对照的比较，我们定义了一组284个妊娠特异性蛋白质组学生物标志物。随后，我们从第28周获得的标本中开发了一个与未来先兆子痫相关的50种生物标志物模型（病例分类因子为1.032 +/- 0.411，对照组为-1.038 +/- 0.432; P < 0.001）。在随后发生先兆子痫的妇女中，分类因子从第12周到第16周到第28周显著增加（n=16;从-0.392 +/- 0.383到1.070 +/- 0.383; P < 0.001），对照组略有下降（n=16;从-0.647 +/- 0.437到-1.024 +/- 0.433; P=0.043）。生物标志物包括纤维蛋白原α链、胶原蛋白α链和尿调蛋白片段。这些标记物似乎在妊娠28周时预测先兆子痫具有良好的置信度，但在更早的时间点（第12-16周和第20周）不可靠。在其他队列中进行前瞻性验证后，这些标志物可能有助于更好地预测，监测和准确诊断先兆子痫。（高血压。2011;57[第2部分]：561-569。
Preeclampsia is a major determinant of fetal and maternal morbidity and mortality. We used a proteomic strategy to identify urinary biomarkers that predict preeclampsia before the onset of disease. We prospectively collected urine samples from women throughout pregnancy. Samples from gestational weeks 12 to 16 (n=45), 20 (n=50), and 28 (n=18) from women who subsequently had preeclampsia develop were matched to controls (n=86, n=49, and n=17, respectively). We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Disease-specific peptide patterns were generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. From comparison with nonpregnant controls, we defined a panel of 284 pregnancy-specific proteomic biomarkers. Subsequently, we developed a model of 50 biomarkers from specimens obtained at week 28 that was associated with future preeclampsia (classification factor in cases, 1.032 +/- 0.411 vs controls, -1.038 +/- 0.432; P < 0.001). Classification factor increased markedly from week 12 to 16 to 28 in women who subsequently had preeclampsia develop (n=16; from -0.392 +/- 0.383 to 1.070 +/- 0.383; P < 0.001) and decreased slightly in controls (n=16; from -0.647 +/- 0.437 to -1.024 +/- 0.433; P=0.043). Among the biomarkers are fibrinogen alpha chain, collagen alpha chain, and uromodulin fragments. The markers appear to predict preeclampsia at gestational week 28 with good confidence but not reliably at earlier time points (weeks 12-16 and 20). After prospective validation in other cohorts, these markers may contribute to better prediction, monitoring, and accurate diagnosis of preeclampsia. (Hypertension. 2011;57[part 2]:561-569.)