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基于串联质量标签的铜宫内节育器相关异常子宫出血患者血清的定量蛋白质组学分析。

Tandem mass tag-based quantitative proteomic profiling of the serum of patients with abnormal uterine bleeding associated with copper intrauterine device.

机构信息

NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Pharmacy, Fudan University, Shanghai, China.

NHC Key laboratory of Birth Defects Prevention (Henan Provincial Research Institute for Population and Family Planning), Henan, China.

出版信息

Int J Gynaecol Obstet. 2021 Jul;154(1):169-178. doi: 10.1002/ijgo.13562. Epub 2021 Jan 13.

Abstract

OBJECTIVE

To investigate changes in the level of protein in serum and uncover the underlying pathogenesis of abnormal uterine bleeding (AUB) associated with copper intrauterine devices (Cu IUD).

METHODS

Protein profiles were investigated via tandem mass tag (TMT)-based quantitative proteomics and bioinformatics technology. Quantification and characterization of candidate proteins were further performed in 33 controls and 45 cases by Luminex assay and enzyme-linked immunosorbent assay.

RESULTS

In total, 842 proteins were identified via TMT coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the serum of individuals with IUDs. Among them, 25 differentially expressed proteins (p < 0.05) were observed, including eight upregulated proteins and 17 downregulated proteins. Ten proteins were verified, and Alpha-1-Antitrypsin (a1AT) had a significantly elevated expression in women with AUB associated with the Cu IUD compared with healthy controls (p = 0.026) and a high area under the curve value (0.656), as well as sensitivity (64.9%) and specificity (71.9%).

CONCLUSION

This is the first study to explore changes in serum protein and the underlying mechanisms of AUB associated with the Cu IUD via TMT technology. a1AT with biomarker potential was validated. These findings might provide an experimental basis for the early diagnosis or treatment of AUB associated with the Cu IUD.

摘要

目的

探讨与含铜宫内节育器(Cu IUD)相关的异常子宫出血(AUB)患者血清蛋白水平的变化,并揭示其潜在的发病机制。

方法

采用串联质量标签(TMT)-基于定量蛋白质组学和生物信息学技术研究蛋白质谱。通过 Luminex 检测和酶联免疫吸附试验(ELISA)进一步对 33 例对照和 45 例病例进行候选蛋白的定量和特征分析。

结果

通过 TMT 联合液相色谱-串联质谱(LC-MS/MS)共鉴定到宫内节育器个体血清中的 842 种蛋白质。其中,观察到 25 种差异表达的蛋白质(p<0.05),包括 8 种上调蛋白和 17 种下调蛋白。对 10 种蛋白质进行了验证,与健康对照组相比,与 Cu IUD 相关的 AUB 妇女的 Alpha-1-Antitrypsin(a1AT)表达显著升高(p=0.026),曲线下面积值(0.656)较高,灵敏度(64.9%)和特异性(71.9%)较高。

结论

这是首次通过 TMT 技术研究与 Cu IUD 相关的 AUB 患者血清蛋白变化及其潜在机制。验证了具有潜在生物标志物的 a1AT。这些发现可能为 Cu IUD 相关的 AUB 的早期诊断或治疗提供实验基础。

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