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通过血浆蛋白质组学鉴定骨科手术患者的血栓生物标志物。

Identification of thrombotic biomarkers in orthopedic surgery patients by plasma proteomics.

机构信息

School of Nursing, Jinan University, Guangzhou, 510613, China.

The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.

出版信息

J Orthop Surg Res. 2023 Mar 21;18(1):222. doi: 10.1186/s13018-023-03672-1.

DOI:10.1186/s13018-023-03672-1
PMID:36944974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10028780/
Abstract

BACKGROUND

Due to the poor specificity of D-dimer, more accurate thrombus biomarkers are clinically needed to improve the diagnostic power of VTE.

METHODS

The plasma samples were classified into low-risk group (n = 6) and high-risk group (n = 6) according to the Caprini Thrombosis Risk Assessment Scale score. Data-independent acquisition mass spectrometry (DIA-MS) was performed to identify the proteins in the 12 plasma samples. Bioinformatics analysis including volcano plot, heatmap, KEGG pathways and chord diagram analysis were drawn to analyze the significantly differentially expressed proteins (DEPs) between the two groups. Then, another 26 plasma samples were collected to verify the key proteins as potential biomarkers of VTE in orthopedic surgery patients.

RESULTS

A total of 371 proteins were identified by DIA-MS in 12 plasma samples. Volcano plotting showed that there were 30 DEPs. KEGG pathway enrichment analysis revealed that the DEPs were majorly involved in the blood coagulation pathway. The chord diagram analysis demonstrated that proteins SAA1, VWF, FLNA, ACTB, VINC, F13B, F13A and IPSP in the DEPs were significantly related to blood coagulation. VWF and F13B were selected for validation experiments. ELISA test showed that, as compared with those in the low-risk group, the level of VWF in the high-risk sera was significantly increased.

CONCLUSIONS

The level of VWF in the high-risk group of thrombosis after orthopedic surgery was significantly higher than that in the low-risk group of preoperative thrombosis, suggesting that VWF may be used as a potential thrombus biomarker in orthopedic surgery patients.

摘要

背景

由于 D-二聚体的特异性较差,临床上需要更准确的血栓生物标志物来提高 VTE 的诊断能力。

方法

根据 Caprini 血栓风险评估量表评分,将血浆样本分为低危组(n=6)和高危组(n=6)。采用数据非依赖采集质谱(DIA-MS)鉴定 12 个血浆样本中的蛋白质。绘制火山图、热图、KEGG 通路和和弦图分析等生物信息学分析,分析两组间差异表达蛋白(DEPs)。然后,收集另外 26 个血浆样本,验证关键蛋白是否为骨科手术患者 VTE 的潜在生物标志物。

结果

通过 DIA-MS 在 12 个血浆样本中鉴定出 371 种蛋白质。火山图显示有 30 个 DEPs。KEGG 通路富集分析显示,DEPs 主要参与了血液凝固途径。和弦图分析表明,DEPs 中的 SAA1、VWF、FLNA、ACTB、VINC、F13B、F13A 和 IPSP 等蛋白与血液凝固密切相关。选择 VWF 和 F13B 进行验证实验。ELISA 试验显示,与低危组相比,高危组血栓形成患者血清中 VWF 水平显著升高。

结论

骨科手术后血栓形成高危组的 VWF 水平明显高于术前血栓形成低危组,提示 VWF 可能作为骨科手术患者潜在的血栓生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/7328f6088c98/13018_2023_3672_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/c0c2841191ec/13018_2023_3672_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/8a120804b07a/13018_2023_3672_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/bd01ef01879f/13018_2023_3672_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/3818183d59cf/13018_2023_3672_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/17ce9ffce107/13018_2023_3672_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/7328f6088c98/13018_2023_3672_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/c0c2841191ec/13018_2023_3672_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/8a120804b07a/13018_2023_3672_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/bd01ef01879f/13018_2023_3672_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/3818183d59cf/13018_2023_3672_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/17ce9ffce107/13018_2023_3672_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cfc/10029257/7328f6088c98/13018_2023_3672_Fig6_HTML.jpg

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