应用蛋白指纹图谱技术筛选原发性胆汁性肝硬化患者血清特异性标志物  

Screening for specific biomarkers in serum for diagnosis of primary biliary cirrhosis using proteomic fingerprint technology

作　　者：胡朝军[1] 李永哲[1] 赵冠飞[1] 李宁 许洋 佟大伟[1] 张蜀澜[1] 

机构地区：[1]中国医学科学院中国协和医科大学,北京协和医院,北京市100730 [2]吴阶平医学基金会,北京市100062

出　　处：《世界华人消化杂志》2008年第3期277-283,共7页World Chinese Journal of Digestology

基　　金：国家自然科学基金;No.30640084;No.30471617~~

摘　　要：目的:探讨蛋白指纹图谱技术筛选原发性胆汁性肝硬化(PBC)患者血清中可用于诊断的特异性标志物.方法:采用弱阳离子纳米磁性微球捕获血清中的蛋白,ProteinChip PBSII-C型蛋白质芯片阅读仪检测绘制成蛋白指纹图谱.所有蛋白指纹图谱采用Biomarker Wizard 3.1分析之后用Biomarker Patterns Software 5.0识别最终可能用于PBC诊断的蛋白标志物并优化组合建立诊断模型.结果:在PBC患者和对照组之间找到69个差异蛋白峰(P<0.05).其中质荷比(m/z)为3445,4260,8133和16290的蛋白峰建立PBC诊断模型.该诊断模型能很好地把PBC患者从其他肝脏疾病患者和正常人群中区分出来,其敏感性为93.3%,特异性为95.1%.经双盲实验验证,该模型对PBC诊断的敏感性为92.9%,特异性为82.4%.结论:采用纳米磁性微球与蛋白质芯片阅读仪联用的蛋白指纹图谱技术可以检测PBC患者血清中的特异性蛋白标志物,并建立敏感性和特异性均较高的PBC诊断模型.AIM： To screen for the potential protein biomarkers in serum for the diagnosis of primary biliary cirrhosis （PBC） using proteomic fingerprint technology. METHODS： Proteomic fingerprint technology combining magnetic beads with MALDI-TOF-MS was used to profile and compare the serum proteins from 44 patients with PBC, 32 patients with other hepatic diseases and 43 healthy blood donors. Proteomic patterns associated with PBC were identified by Biomarker Patterns Software. Model of biomarkers was constructed and evaluated using the Biomarker Patterns Software. RESULTS： A total of 69 discriminating m/z peaks were identified that were related to PBC （P 〈 0.05）. The model of biomarkers constructed by the Biomarker Patterns Software based on the four biomarkers （3445, 4260, 8133 and 16 290） generated excellent separation between the PBC and control groups. The sensitivity was 93.3% and the specificity was 95.1%. Blind test data indicated a sensitivity of 92.9% and a specificity of 82.4%. CONCLUSION： Biomarkers for PBC can be discovered in serum by MALDI-TOF-MS combining the use of magnetic beads. The pattern of combined markers provides a powerful and reliable diagnostic method for PBC with a high sensitivity and specificity.

关 键 词：原发性胆汁性肝硬化 自身免疫性肝炎 生物标志物 磁性微球 蛋白指纹图谱技术 

分 类 号：R575.2[医药卫生—消化系统]