Study on serum peptidome profiling of primary biliary cirrhosis using MALDI-TOF-MS
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摘要:
目的应用弱阳离子交换磁珠提取多肽结合基质辅助激光解析电离飞行时间质谱系统(MALDI-TOF-MS)分析原发性胆汁性肝硬化(PBC)患者的血清多肽谱,寻找具有潜在意义的血清标志物。方法收集105例血清样本,包括55例PBC患者、25例其他肝病患者和25例正常对照者血清样本,经弱阳离子交换磁珠纯化,MALDI-TOF-MS分析及ClinProTools生物信息学方法研究其血清多肽表达谱。结果在质荷比(m/z)1000~10 000 Da的范围内3组间共检测到158个血清多肽峰,其中83个有统计学意义(P<0.001),在PBC中表达上调的多肽有31个,表达下调的多肽有52个。组合m/z 1062.47、5356.13、4268.63、846.18、1945.31和6649.53Da 6个峰建立多肽诊断指纹图谱模型,该模型盲样验证的准确率在PBC组、正常对照组和其他肝病组分别为100%、81.8%和72.7%。结论可以利用MALDI-TOF-MS技术和ClinProTools软件来筛选PBC血清标志物,其在PBC诊断方面具有一定的价值。
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关键词:
- 肝硬化,胆汁性 /
- 光谱法,质量,基质辅助激光解吸电离 /
- 血清多肽谱
Abstract:Objective To study serum peptidome profiling using Weak Cation Exchange (WCX) magnetic bead based sample fractionation method combined with matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) technology and to seek potential serum biomarkers of primary biliary cirrhosis.Methods 105 serum samples were collected from 55 patients with PBC, 25 patients with other liver disease and 25 normal controls.These serum samples were enriched by WCX magnetic bead, and the serum peptidome profiling was recognized using MALDI-TOF-MS and ClinProTools bioinformatics software was used for statistical analysis.Results 158 peptide peaks were obtained with the mass charge ratio (m/z) value ranging from 1 000 to 10 000 among the three groups.Among these peaks, 83 peptide peaks was statistically significant (P<0.001) , 31 were up-regulated and 52 down-regulated.Six peaks with m/z1062.47 Da, 5356.13 Da, 4268.63 Da, 846.18 Da, 1945.31 Da and 6649.53 Da were observed in the peptide fingerprint model.The model accuracy in blind test was 100%, 81.8% and 72.7% among PBC group, normal control group and other liver disease group, respectively.Conclusion MALDI-TOF-MS combined with ClinProTools software can be a tool to identify the biomarkers of PBC.It can be of some value to the diagnosis of PBC.
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Key words:
- liver cirrhosis /
- biliary /
- spectrometry
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