用飞行质谱技术筛选肝棘球蚴病患者血清蛋白质组学标记物  

Serum proteomic marker of hepatic echinococcosis screened by surface enhanced laser desorption/ionization time of flight mass spectrometry

作　　者：孟存仁[1] 张琼[1] 张朝霞[1] 王庆荣[1] 薛黎[1] 曹玲[1] 

机构地区：[1]新疆医科大学第一附属医院医学检验中心,乌鲁木齐830054

出　　处：《中国地方病学杂志》2010年第4期461-465,共5页Chinese Jouranl of Endemiology

摘　　要：目的 筛选肝棘球蚴病患者血清蛋白质组学标记物,建立血清蛋白质指纹图诊断模型,评价其应用价值.方法 肝棘球蚴病患者68例,对照组73例（其他肝病患者33例,健康人40例）,将全部样品分为训练组（37例）和测试组（67例）.用弱阳离子交换蛋白芯片结合表面增强激光解析电离飞行时间质谱（SELDI-TOF-MS）技术检测肝棘球蚴病患者和对照者的血清蛋白质谱.分别比较训练组中37例肝棘球蚴患者和37例对照者、5例肝囊型棘球蚴病（HCE）患者和5例肝泡球蚴病（HAE）患者、8例肝棘球蚴病患者手术前后两组血清蛋白质峰的差异.利用ZJU-PDAS软件进行数据处理,通过支持向量机（SVM）运算建立蛋白质指纹图诊断模型,并用测试组标本采用盲法对模型的灵敏度和特异度进行验证.结果 肝棘球蚴病组和对照组共筛选出9个差异蛋白峰,其中相对分子质量为1044、1047、1073、1075、1338、6453、6649、8714 m/z的8个蛋白质峰在病例组中下调,相对分子质量为5651 m/z的蛋白峰在病例组中上调（P〈0.05）,盲法验证表明所建模型对肝棘球蚴病诊断的灵敏度为77.4%（24/31）,特异度为66.7%（24/36） 阳性预测值为66.7%（24/36）,阴性预测值为77.4%（24/31）.HCE和HAE患者之间筛选出2个差异表达蛋白峰,质荷比分别为8716和2751 m/z（P〈0.05） 8例肝棘球蚴病患者手术前后两组共筛选出6个差异表达蛋白质峰,相对分子质量分别为1297、1505、1525、1534、5921,5941 m/z（P〈0.05）.结论 SELDI-TOF-MS技术结合生物信息学方法能筛选出肝棘球蚴病患者血清蛋白质组学标记物,对肝棘球蚴病诊断及预后判断具有潜在的应用价值.Objective To screen serum proteomic marker of hepatic echinococcosis, establish a diagnotic model of serum protein fingerprint patterns, and evaluate its clinical application for hepatic echinococcosis. Methods Serum samples from 68 patients with hepatic echinococcosis matched with 73 controls composed of 33 patients with liver diseases other than hepatic echinococcosis and 40 healthy people were collected. All subjects were divided into training group （37） and testing group （67）. Serum protein profiling of patients with hepatic echinococcosis and controls were detected using surface enhanced laser desorption/ionization time of flight mass spectrometry（SELDI-TOF-MS） and weak cation exchange protein chip（WCX2）. Peak intensities were compared, in the training group, between 37 patients with hepatic echinococcosis and 37 controls, 5 patients with HCE and 5 patients with HAE, and 8 patients with hepatic echinococcosis before and after operation, respectively. ZJU-Protein Chip Data Analyze System（ZJU-PDAS） was used for data analysis and the model of serum protein fingerprint patterns was build by support vector machine （SVM）. The sensitivity and specificity of the model for diagnosis of hepatic echinococcosis were verified by blind method on samples of testing group. Results There were nine different protein peak spectra between hepatic echinococcosis group and control group, of which eight protein peak spectra decreased in patient group, their relative molecular mass were 1044, 1047, 1073, 1075, 1338, 6453, 6649, 8714 m/z, respectively, while one protein peak spectrum（5651 m/z） increased（P 〈 0.05）. The sensitivity,specificity, positive predictive and negative predictive value of the model validated by blind method were 77.4% （24/31）, 66.7% （24/36）, respectively. There were two different protein peak spectra between HCE group and HAE group, Their relative molecule mass were 8716 and 2751 m/z, respectively （P 〈 0.05）. Six different proteins were detected from pre-operatio

关 键 词：棘球蚴病 肝 蛋白质组学 表面增强激光解析电离飞行时间质谱 灵敏度 特异度 

分 类 号：R686[医药卫生—骨科学]