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使用iTRAQ定量蛋白质组学鉴定妊娠早期预测妊娠期糖尿病的候选生物标志物。

Identification of candidate biomarkers for the prediction of gestational diabetes mellitus in the early stages of pregnancy using iTRAQ quantitative proteomics.

作者信息

Zhao Danqing, Shen Liming, Wei Yan, Xie Jiaming, Chen Shuqiang, Liang Yi, Chen Youjiao, Wu Haorong

机构信息

Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, P. R. China.

Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, P. R. China.

出版信息

Proteomics Clin Appl. 2017 Jul;11(7-8). doi: 10.1002/prca.201600152. Epub 2017 Apr 24.

Abstract

PURPOSE

Gestational diabetes mellitus (GDM) is one of the most common medical problems of pregnancy. This study is designed to identify serum biomarkers, which can predict the subsequent development of GDM at early stages.

EXPERIMENTAL DESIGN

Maternal blood was obtained prospectively from pregnant women at 12-16 wk of pregnancy. Among these, 30 women were subsequently diagnosed with GDM at 24 to 28 wk and were selected as case studies along with 30 normoglycemic women as controls. Serum samples were analyzed by using iTRAQ analysis.

RESULTS

Thirty three differentially expressed proteins were identified between case and control groups. They were involved in various signaling processes previously implied in GDM. Of which four proteins, i.e. apolipoprotein E, coagulation factor IX, fibrinogen alpha chain, and insulin-like growth factor-binding protein 5 were successfully verified by ELISA. Combinations of these four proteins, the area under the receiver operating characteristic curve, sensitivity, and specificity were 0.985, 80% and 95%, respectively.

CONCLUSION

The results highlight the roles of complement system, inflammatory and immune response, and blood coagulation in the pathogenesis of GDM. The panel of four candidate proteins could distinguish women subsequently developed with GDM from controls with high sensitivity and specificity.

摘要

目的

妊娠期糖尿病(GDM)是孕期最常见的医学问题之一。本研究旨在识别血清生物标志物,以在早期预测GDM的后续发展。

实验设计

前瞻性地收集妊娠12 - 16周孕妇的母血。其中,30名女性随后在24至28周被诊断为GDM,并被选作病例研究,同时选取30名血糖正常的女性作为对照。血清样本采用iTRAQ分析进行检测。

结果

病例组和对照组之间鉴定出33种差异表达蛋白。它们参与了先前GDM中涉及的各种信号传导过程。其中四种蛋白,即载脂蛋白E、凝血因子IX、纤维蛋白原α链和胰岛素样生长因子结合蛋白5,通过酶联免疫吸附测定(ELISA)成功验证。这四种蛋白组合的受试者工作特征曲线下面积、敏感性和特异性分别为0.985、80%和95%。

结论

结果突出了补体系统、炎症和免疫反应以及血液凝固在GDM发病机制中的作用。四种候选蛋白组合能够以高敏感性和特异性区分随后发生GDM的女性与对照组。

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