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Prediction of invasive placenta through cell-free RNA analysis

通过无细胞 RNA 分析预测侵入性胎盘

基本信息

批准号：
20791169
负责人：
SHIHO Yoshimura
金额：
$ 2.75万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

项目摘要

To develop the strategy predicting the invasive placenta, we have been collecting over 660 blood samples. However, since nobody have complicated with invasive placenta in the cases, we could not assess the predictive markers for invasive placenta. Therefore, we employed to predict the preeclampsia. The objective of this study is to predict occurrence of preeclampsia in a series of patients at gestational week 15-20 using a panel of cell-free or cellular mRNA markers. Data from 62 preeclamptic patients asymptomatic at the time of blood testing and 310 controls were analyzed. Multivariable analysis was performed using discriminant analysis. In the analysis of cell-free RNA, univariable analysis identified vascular endothelial growth factor receptor 1 (FLT1) as the marker with the highest detection rate, and placenta-specific-1 with the lowest. Mean estimated score for preeclampsia was 9.4 for controls and 72.5 for subjects who developed preeclampsia. An ROC curve obtained using the estimated score for preeclampsia as test variable yielded a DR of 84% (95%CI 71.8-91.5) at a 5% false-positive rate with an area under the curve of 0.927 (p<0.001). Again, DR and score for each patient for classification as preeclamptic correlated with severity. Next, in the cellular RNA analysis, the univariate ROC analysis identified soluble Flt-1 and endoglin as the markers with the highest sensitivity. The best multivariable model was obtained by combining Flt-1, Endoglin, placenta growth factor (PlGF) and parity. The relative ROC curve yielded a sensitivity of 66% at a 10% 1-specificity rate with an area under the curve of 0.884 (p<0.001). In conclusion, a panel of cell-free or cellular mRNA is able to detect subjects who will develop preeclampsia.

为了制定预测侵入性胎盘的策略，我们收集了660多份血液样本。但由于病例中无一例合并侵袭性胎盘，故无法评估侵袭性胎盘的预测指标。因此，我们采用预测子痫前期。本研究的目的是使用一组无细胞或细胞mRNA标记物预测妊娠15-20周的一系列患者中先兆子痫的发生。分析了62名在血液检测时无症状的先兆子痫患者和310名对照者的数据。采用判别分析进行多变量分析。在无细胞RNA分析中，单变量分析确定血管内皮生长因子受体1（FLT 1）为检出率最高的标志物，胎盘特异性-1检出率最低。对照组的先兆子痫平均估计评分为9.4，发生先兆子痫的受试者为72.5。以先兆子痫的估计评分作为测试变量，得到的ROC曲线显示，在5%的假阳性率下，DR为84%（95%CI 71.8-91.5），曲线下面积为0.927（p<0.001）。再次，DR和评分为每个患者的分类为先兆子痫与严重程度相关。接下来，在细胞RNA分析中，单变量ROC分析将可溶性Flt-1和内皮糖蛋白鉴定为具有最高灵敏度的标志物。通过组合Flt-1、Endoglin、胎盘生长因子（PlGF）和产次获得最佳多变量模型。相对ROC曲线的敏感性为66%，特异性为10%，曲线下面积为0.884（p<0.001）。总之，一组无细胞或细胞mRNA能够检测将发展先兆子痫的受试者。