子痫前期孕妇血清中血管炎性蛋白的表达与潜在生物标志物分析

Expression of vascular inflammatory proteins in preeclamptic women and potential biomarkers for preeclampsia analysis

目的通过测定子痫前期血清中相关血管炎性蛋白的表达特征以发掘子痫前期潜在预测标志物。方法首先采用病例对照研究募集2017年9月至2018年9月于复旦大学附属妇产科医院就诊的子痫前期孕妇和同期血压正常的对照组孕妇,基于多因子流式检测技术测定孕妇血清中12种相关血管炎性蛋白的浓度。通过非参数t检验进行差异性分析以寻找子痫前期相关血管炎性蛋白。然后,从复旦大学附属妇产科医院组织库中获取具有子痫前期高危因素的孕早期孕妇血清标本,并测定子痫前期相关血管炎性因子的血清浓度,通过受试者工作特征(receiver operating characteristic,ROC)曲线分析评估子痫前期相关血管炎症因子的预测价值。结果39例子痫前期和43例对照孕妇血清测定了10个血管炎症蛋白的浓度。结果显示,血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)和肌红蛋白在子痫前期孕妇血清中显著升高,而基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)显著降低。在96例具有子痫前期高危因素的孕早期孕妇血清中测定上述分子的浓度并进行ROC曲线分析,结果显示VCAM-1预测孕晚期子痫发生的曲线下面积(the area under the curve,AUC)达到了0.802,而肌红蛋白和MMP-9不能显著预测子痫前期的发生。结论子痫前期患者中部分血管炎性蛋白表达异常,VCAM-1可能是孕早期子痫前期风险预测的生物标志物。

Objective To explore potential predictive biomarkers for preeclampsia by analyzing the expression and characteristics of vascular-related inflammatory proteins in the serum of preeclamptic pregnant women.Methods A case-control study was conducted from Sep 2017 to Sep 2018 in the Obstetrics and Gynecology Hospital,Fudan University.Preeclamptic pregnant women and normotensive pregnant controls during the same period were recruited.The concentration of 12 vascular inflammation-related proteins in the patients’serum was determined by multiplex flow cytometry.The vascular-related inflammatory molecules were subjected to differential analysis by non-parametric t-test to obtain preeclampsia-related vascular inflammatory proteins.Finally,high-risk preeclampsia pregnancy serum samples from the biobank were retrieved.Serum concentrations of preeclampsia-related vascular inflammatory proteins were determined,and receiver operating characteristic(ROC)curve analysis was conducted for preliminary predictive assessment of preeclampsia.Results This study conducted a quantitative analysis of serum vascular inflammatory proteins in 39 cases of preeclampsia and 43 cases of control pregnant women,detecting 10 vascular inflammatory proteins expressed in maternal serum.Among these,myoglobin and vascular cell adhesion molecule-1(VCAM-1)exhibited significant elevation in the serum of preeclamptic pregnant women,while matrix metalloproteinase-9(MMP-9)showed a marked decrease.ROC curve analysis revealed that in 96 high-risk early pregnancy women,the area under the curve(AUC)for VCAM-1 reached 0.802,whereas myoglobin and MMP-9 did not significantly predict the occurrence of preeclampsia.Conclusion Preeclampsia patients exhibit abnormal expression of serum inflammatory proteins,among which VCAM-1 may be a potential biological marker for early pregnancy preeclampsia risk prediction.