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通过蛋白质组学鉴定新生儿尿液生物标志物:在梗阻性肾病中的应用

Identification of urinary biomarkers by proteomics in newborns: use in obstructive nephropathy.

作者信息

Decramer Stephane, Zürbig Petra, Wittke Stefan, Mischak Harald, Bascands Jean-Loup, Schanstra Joost P

机构信息

Inserm, U858,and Université Toulouse III Paul Sabatier, IFR31, Institut Louis Bugnard, Toulouse, France.

出版信息

Contrib Nephrol. 2008;160:127-141. doi: 10.1159/000125956.

Abstract

An important issue in congenital unilateral ureteropelvic junction (UPJ) obstruction, a frequent pathology in newborns, is whether infants should undergo surgery. Non-invasive biomarkers to reduce or replace the current invasive clinical exploration are not available. The objective of this study was to identify urinary markers of UPJ obstruction. We compared a number of proteome technologies to study the urinary proteome in UPJ obstruction and selected online capillary electrophoresis coupled to mass-spectrometry for the selection of non-invasive prognostic biomarkers. We selected 53 urinary biomarkers that were able to distinguish between different levels of UPJ obstruction. In a prospective study using these 53 biomarkers, we predicted with 97% accuracy, and several months in advance, the clinical outcome of 36 UPJ-obstruction patients. Some of the discriminating biomarkers were identified. A newly identified marker, proSAAS (proprotein convertase subtilisin/kexin type 1 inhibitor), generated a new hypothesis in the physiopathology of UPJ obstruction. These results show that analysis of urinary polypeptides in newborns with UPJ obstruction can predict their clinical outcome.

摘要

先天性单侧输尿管肾盂连接部(UPJ)梗阻是新生儿常见的病理状况,其中一个重要问题是婴儿是否应接受手术。目前尚无用于减少或替代当前侵入性临床检查的非侵入性生物标志物。本研究的目的是识别UPJ梗阻的尿液标志物。我们比较了多种蛋白质组技术来研究UPJ梗阻患者的尿液蛋白质组,并选择了在线毛细管电泳与质谱联用技术来筛选非侵入性预后生物标志物。我们筛选出53种能够区分不同程度UPJ梗阻的尿液生物标志物。在一项使用这53种生物标志物的前瞻性研究中,我们提前数月以97%的准确率预测了36例UPJ梗阻患者的临床结局。部分具有鉴别作用的生物标志物得到了识别。一种新发现的标志物,即前SAAS(前蛋白转化酶枯草杆菌蛋白酶/kexin 1型抑制剂),为UPJ梗阻的病理生理学提出了新的假说。这些结果表明,对患有UPJ梗阻的新生儿进行尿液多肽分析可以预测其临床结局。

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