Pregnancy associated plasma protein-A2: a novel biomarker for Down syndrome.

Pregnancy associated plasma protein-A2: a novel biomarker for Down syndrome.
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DOI:
10.1016/j.placenta.2014.08.001
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发表时间:
2014-11
期刊:
影响因子:
3.8
通讯作者:
Reznik, S. E.
Reznik, S. E.
中科院分区:
医学3区
文献类型:
--
作者:
Munnangi, S.;Gross, S. J.;Madankumar, R.;Salcedo, G.;Reznik, S. E.

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为了改善21三体的产前筛查,我们评估了妊娠相关血浆蛋白-A2(PAPP-A2)作为21三体的一种潜在的新的中期妊娠生物标志物。三体21和正常对照中期妊娠胎盘样品进行定量RT PCR分析的七个基因,我们以前发现是在三体21胎盘差异表达。应用免疫组织化学方法检测PAPP-A2在正常妊娠和21三体妊娠中孕胎盘中的定位和差异表达。通过蛋白质印迹法比较了10例21三体和10例二倍体妊娠中的PAPP-A2母体血清蛋白水平。采用酶联免疫吸附法(ELISA)检测30例唐氏综合征患者和142例正常对照者血清PAPP-A2水平。使用回归分析来确定PAPP-A2与21三体的其他现有标志物的相关性。与二倍体胎盘相比,唐氏综合症胎盘中PAPP-A2(又名PLAC 3)mRNA和蛋白质表达均增加。与二倍体妊娠相比,唐氏综合征妊娠的母体血清中PAPP-A2也增加。PAPP-A2表达与已建立的标记物弱相关。这项工作利用了我们以前进行的系统方法,发现新的母体血清生物标志物的三体21,使用cDNA微阵列分析。从验证微阵列结果开始,我们追踪了唐氏综合征中从胎盘mRNA到母体血清蛋白的PAPP-A2过表达。PAPP-A2可作为产前筛查21三体的一个额外的母体血清标志物。
In an effort to improve prenatal screening for Trisomy 21, we evaluated pregnancy associated plasma protein-A2 (PAPP-A2) as a potential novel second trimester biomarker for Trisomy 21. Trisomy 21 and normal control mid-trimester placental samples were subjected to quantitative rt PCR analysis of seven genes we had previously found to be differentially expressed in Trisomy 21 placentae. The localization and differential expression of PAPP-A2 in second trimester placentae from normal and Trisomy 21 pregnancies was determined by immunohistochemistry. PAPP-A2 maternal serum protein levels in ten Trisomy 21 and ten diploid pregnancies were compared by Western blotting. Maternal serum PAPP-A2 levels were measured in 30 Down syndrome cases and 142 normal controls, using ELISA. Regression analysis was used to determine the correlation of PAPP-A2 with other existing markers of Trisomy 21. PAPP-A2 (aka PLAC3) mRNA and protein expression were both increased in Down syndrome placentae as compared to diploid placentae. PAPP-A2 was also increased in maternal serum from Down syndrome pregnancies as compared to diploid pregnancies. PAPP-A2 expression correlated weakly with established markers. This work takes advantage of our previously performed systematic approach to the discovery of novel maternal serum biomarkers for Trisomy 21, using cDNA microarray analysis. Beginning with the validation of the microarray results, we have tracked PAPP-A2 overexpression in Down syndrome from placental mRNA to maternal serum protein. PAPP-A2 could serve as an additional maternal serum marker in prenatal screening for Trisomy 21.
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