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基于无标记定量技术的原发性血小板增多症患者血小板活化相关差异蛋白分析

[Analysis of Differential Proteins Related to Platelet Activation in Patients with Essential Thrombocythemia Based on Label-Free Quantitative Technology].

作者信息

Li Yu-Jin, Ma Ju-Ning, Wang Zi-Qin, Yang Er-Peng, Wang Ming-Jing, Ming Jing, Wang De-Hao, Niu Ji-Cong, Liu Wei-Yi, Hu Xiao-Mei

机构信息

Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.

Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Jun;30(3):836-843. doi: 10.19746/j.cnki.issn.1009-2137.2022.03.028.

Abstract

OBJECTIVE

To analysis the specific protein markers of essential thrombocythemia (ET) based on proteomics technology, to explore and verify the differential protein related to platelet activation.

METHODS

Blood samples were obtained from ET patients and healthy people and a certain protein mass spectrometry was detected using label-free quantitative technology. The proteins relative abundance increased or down-regulated by 1.3 times in the disease group compared with the control group, and the protein abundance in the two groups t test P<0.05 were defined as differential proteins. Bioinformatics analysis of the differential proteins was performed using GO and KEGG. The difference in the average protein abundance between the two groups was analyzed by t test and P<0.05 was considered statistically significant. Differential proteins were selected for verification by parallel reaction monitoring (PRM) technology.

RESULTS

A total of 140 differential proteins were found, of which 72 were up-regulated and 68 were down-regulated. KEGG enrichment showed that the differential protein expression was related to the platelet activation pathway. The differential proteins related to platelet activation were GPV, COL1A2, GP1bα, COL1A1 and GPVI. Among them, the expressions of GPV, GP1bα and GPVI were up-regulated, and the expressions of COL1A2 and COL1A1 were down-regulated. PRM verification of COL1A1, GP1bα, GPVI and GPV was consistent with LFP proteomics testing.

CONCLUSION

Differential proteins in ET patients are related to platelet activation pathway activation.Differential proteins such as GPV, GPVI, COL1A1 and GP1bα can be used as new targets related to ET platelet activation.

摘要

目的

基于蛋白质组学技术分析原发性血小板增多症(ET)的特异性蛋白质标志物,探索并验证与血小板活化相关的差异蛋白质。

方法

采集ET患者和健康人的血液样本,采用无标记定量技术检测特定蛋白质质谱。疾病组中相对丰度较对照组增加或下调1.3倍,且两组蛋白质丰度t检验P<0.05的蛋白质定义为差异蛋白质。使用GO和KEGG对差异蛋白质进行生物信息学分析。采用t检验分析两组间平均蛋白质丰度差异,P<0.05认为具有统计学意义。选择差异蛋白质通过平行反应监测(PRM)技术进行验证。

结果

共发现140种差异蛋白质,其中72种上调,68种下调。KEGG富集显示差异蛋白质表达与血小板活化途径相关。与血小板活化相关的差异蛋白质为GPV、COL1A2、GP1bα、COL1A1和GPVI。其中,GPV、GP1bα和GPVI表达上调,COL1A2和COL1A1表达下调。COL1A1、GP1bα、GPVI和GPV的PRM验证结果与LFP蛋白质组学检测一致。

结论

ET患者的差异蛋白质与血小板活化途径激活相关。GPV、GPVI、COL1A1和GP1bα等差异蛋白质可作为与ET血小板活化相关的新靶点。

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