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用于子痫前期和胎儿生长受限早期检测的母体尿液蛋白质组学分析

Proteomic Analysis of Maternal Urine for the Early Detection of Preeclampsia and Fetal Growth Restriction.

作者信息

Bujold Emmanuel, Fillion Alexandre, Roux-Dalvai Florence, Scott-Boyer Marie Pier, Giguère Yves, Forest Jean-Claude, Gotti Clarisse, Laforest Geneviève, Guerby Paul, Droit Arnaud

机构信息

CHU de Québec-Université Laval Research Center, Université Laval, Quebec City, QC G1V 4G2, Canada.

Department of Obstetrics and Gynecology, Faculty of Medicine, CHU de Québec-Université Laval, Quebec City, QC G1V 4G2, Canada.

出版信息

J Clin Med. 2021 Oct 13;10(20):4679. doi: 10.3390/jcm10204679.

DOI:10.3390/jcm10204679
PMID:34682802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8537852/
Abstract

BACKGROUND

To explore the use of maternal urine proteome for the identification of preeclampsia biomarkers.

METHODS

Maternal urine samples from women with and without preeclampsia were used for protein discovery followed by a validation study. The targeted proteins of interest were then measured in urine samples collected at 20-24 and 30-34 weeks among nine women who developed preeclampsia, one woman with fetal growth restriction, and 20 women with uncomplicated pregnancies from a longitudinal study. Protein identification and quantification was obtained using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

RESULTS

Among the 1108 urine proteins quantified in the discovery study, 21 were upregulated in preeclampsia and selected for validation. Nineteen (90%) proteins were confirmed as upregulated in preeclampsia cases. Among them, two proteins, ceruloplasmin and serpin A7, were upregulated at 20-24 weeks and 30-34 weeks of gestation ( < 0.05) in cases of preeclampsia, and could have served to identify 60% of women who subsequently developed preeclampsia and/or fetal growth restriction at 20-24 weeks of gestation, and 78% at 30-34 weeks, for a false-positive rate of 10%.

CONCLUSIONS

Proteomic profiling of maternal urine can differentiate women with and without preeclampsia. Several proteins including ceruloplasmin and serpin A7 are upregulated in maternal urine before the diagnosis of preeclampsia and potentially fetal growth restriction.

摘要

背景

探讨母体尿液蛋白质组在子痫前期生物标志物识别中的应用。

方法

收集子痫前期患者和非子痫前期患者的母体尿液样本进行蛋白质发现研究,随后进行验证研究。然后,在一项纵向研究中,对9例发生子痫前期的女性、1例胎儿生长受限的女性和20例正常妊娠女性在孕20 - 24周和30 - 34周采集的尿液样本中,测量感兴趣的目标蛋白。使用液相色谱 - 串联质谱法(LC-MS/MS)进行蛋白质鉴定和定量。

结果

在发现研究中定量的1108种尿液蛋白质中,有21种在子痫前期上调并被选作验证。19种(90%)蛋白质在子痫前期病例中被确认为上调。其中,两种蛋白质,铜蓝蛋白和丝氨酸蛋白酶抑制剂A7,在子痫前期病例的妊娠20 - 24周和30 - 34周时上调(P<0.05),它们可用于识别60%在妊娠20 - 24周后发生子痫前期和/或胎儿生长受限的女性,在30 - 34周时为78%,假阳性率为10%。

结论

母体尿液蛋白质组分析可区分子痫前期患者和非子痫前期患者。包括铜蓝蛋白和丝氨酸蛋白酶抑制剂A7在内的几种蛋白质在子痫前期及潜在的胎儿生长受限诊断前,在母体尿液中上调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/132942bbee21/jcm-10-04679-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/2bd65a2d9069/jcm-10-04679-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/91ddd76b455d/jcm-10-04679-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/0be23c1abd32/jcm-10-04679-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/487f93112bd9/jcm-10-04679-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/b6e4ae303b2e/jcm-10-04679-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/132942bbee21/jcm-10-04679-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/2bd65a2d9069/jcm-10-04679-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/91ddd76b455d/jcm-10-04679-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/0be23c1abd32/jcm-10-04679-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/487f93112bd9/jcm-10-04679-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/b6e4ae303b2e/jcm-10-04679-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6729/8537852/132942bbee21/jcm-10-04679-g006.jpg

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