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肝硬化合并门静脉血栓患者的差异蛋白筛选
Screening for differentially expressed proteins in patients with liver cirrhosis complicated by portal vein thrombosis
文章发布日期:2017年12月09日  来源:  作者:熊静平,彭媛媛,张跃新  点击次数:502次  下载次数:76次

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【摘要】:目的 筛选肝硬化合并门静脉血栓形成(PVT)患者的血清差异表达蛋白。方法 收集2015年11月-2016年11月在新疆医科大学第一附属医院感染疾病中心住院的45例肝硬化患者血清标本,其中合并PVT患者22例,无PVT患者23例。采用相对和绝对同位素定量标记(iTRAQ)联合色谱质谱技术筛选两组患者的血清差异蛋白,并对差异蛋白进行生物信息学分析。非正态分布的计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ2检验。采用Fisher确切检验比较各个GO分类或KEGG通路在目标蛋白质集合和总体蛋白质集合中的分布情况,以此评价某个GO term或KEGG通路蛋白质富集度的显著性水平。结果 共筛选出800个蛋白。有差异的蛋白86个,其中32个蛋白上调(ratio≥1.2,P<0.05),54个蛋白下调(ratio≤0.83,P<0.05)。在这些蛋白中,有14类蛋白与细胞组分有关,22类蛋白与生化过程有关,10类蛋白与分子功能有关。使用KEGG分析发现肝硬化合并PVT组较无PVT组有18个蛋白在5个代谢和信号通路中有显著的差异。5个代谢和信号通路分别与脂肪消化和吸收、血小板激活、乙醛酸及二羧酸代谢、破骨细胞分化、轴突导向有关。结论 iTRAQ联合色谱质谱技术能够有效筛选血清差异蛋白,其中GP5、FGA、FGG可能为肝硬化发生PVT的潜在生物标志物,值得进一步研究。
【Abstract】:Objective To investigate the differentially expressed serum proteins in patients with liver cirrhosis complicated by portal vein thrombosis (PVT). Methods Serum samples were collected from 45 patients with liver cirrhosis who were hospitalized in Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, from November 2015 to November 2016, and among these patients, 22 had PVT and 23 had no PVT. Isobaric tags for relative and absolute quantitation (iTRAQ) combined with chromatography and mass spectrometry were used to screen out the differentially expressed serum proteins, and a bioinformatics analysis was performed for the differentially expressed proteins. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The Fisher′s exact test was used to compare the distribution of GO terms or KEGG pathways in the target protein set or total protein set, in order to evaluate the significance level of protein enrichment of a GO term or KEGG pathway. Results A total of 800 proteins were screened out, among which 86 were differentially expressed, including 32 upregulated proteins (ratio ≥1.2, P<0.05) and 54 downregulated proteins (ratio ≤0.83, P<0.05). Among these proteins, 14 were associated with cellular component, 22 were involved in biochemical processes, and 10 were associated with molecular function. The KEGG analysis showed that there were significant differences in 18 proteins in 5 metabolic and signaling pathways between the liver cirrhosis-PVT group and liver cirrhosis group. These 5 metabolic and signaling pathways were associated with fat digestion and absorption, platelet activation, metabolism of glyoxylic acid and dicarboxylic acid, osteoclast differentiation, and axon guidance. Conclusion iTRAQ combined with chromatography and mass spectrometry can effectively screen out the differentially expressed serum proteins, among which GP5, FGA, and FGG may be potential biological markers for PVT in patients with liver cirrhosis and are worthy of further research.
【关键字】:肝硬化;静脉血栓形成;蛋白质组学
【Key words】:liver cirrhosis; venous thrombosis; proteomics
【引证本文】:XIONG JP, PENG YY, ZHANG YX. Screening for differentially expressed proteins in patients with liver cirrhosis complicated by portal vein thrombosis[J]. J Clin Hepatol, 2018, 34(1): 112-117. (in Chinese)
熊静平, 彭媛媛, 张跃新. 肝硬化合并门静脉血栓患者的差异蛋白筛选[J]. 临床肝胆病杂志, 2018, 34(1): 112-117.

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