应用纳米磁珠联合MALDI-TOF-MS技术对双相情感障碍患者血清蛋白质组学的初步研究

摘要

目的 探讨双相情感障碍( Bipolar Disorder,BD)患者血清蛋白质的组学特征,筛选BD特征性生物标志物.方法 选择BD患者40例,其他精神病患者44例和正常健康人43例,用弱阳离子交换(Weak Cationic Exchange,WCX)纳米磁珠捕获血清蛋白质组分,用MALDI - TOF - MS(Matrix Assisted Laser Desorption Ionization Time Of Flight Mass Spectrometer)检测各样品的蛋白质质谱,用Biomarker Wizard 3.1和Biomarker pattems Software5.0软件进行数据分析.结果 在BD组和健康对照组之间筛查到36个差异分子(P＜0.05),从中筛选出17个差异表达蛋白分子(P＜0.01),质荷比(M/Z)分别为M1033.59,M3982.26,M4835.04,M5144.47,M5870.30,M5952.74, M5997.18, M6643.93,M6706.41,M7792.76,M7852.13,M8152.38,M9301.77,M9508.99,M9727.00,M10847.90,M111357.0的分子建立了BD的诊断模型,其敏感性和特异性分别为95.0％和90.7％.对76例新样本的盲法验证结果显示,该模型对BD患者的诊断敏感性为88.5％,特异性为87.0％.结论 采用WCX纳米磁珠与MALDI - TOF - MS联用的技术,可以得到BD特征性血清蛋白质/肽指纹图谱并能够建立敏感性和特异性均较高的BD诊断模型.%Objective To explore the serum proteomic features and to screen the specific serum biomarkers in patients with bipolar disorder (BD). Methods 40 patients with BD, 44 patients with other psychiatric disorders and 43 healthy controls were involved in the study. Weak cationic exchange ( WCX) nanometer magnetic beads were used to capture the serum proteomic components. The proteomic image was detected by using the matrix - assisted laser desorption - ionization time - of - flight mass spectrometry ( MALDI - TOF - MS). Biomarker Wizard 3. 1 and Biomarker patterns Software 5.0 were used to conduct the data analysis. Results A total of 36 discriminating protein molecules related with BD were identified when compared with the healthy controls (P < 0. 05 ). 17 differential expression protein molecules (the mass - to - charge ratio was Ml033. 59, M3982. 26, M4835. 04, M5144. 47, M5870.30, M5952. 74, M5997. 18, M6643. 93, M6706. 41, M7792. 76, M7852. 13, M8152. 38, M9301. 77, M9508.99, M9727. 00, M10847. 90, Ml 11357. 00 respectively) constructed the diagnostic model of BD. The sensitivity was 95. 0% and the specificity was 90. 7%. Blind test carried out in 76 validation samples generated a sensitivity of 88.5% and a specificity of 87.0%. Conclusion The combined use of WCX nanometer magnetic beads and MALDI - TOF - MS is helpful to obtain the specific proteomic image of BD, which may contribute to construct the BD diagnostic model with satisfactory sensitivity and specificity.