精神分裂症患者血清蛋白标志物的临床应用研究

The study on clinical application of serum proteins as biological markers of schizophrenia.

目的应用临床蛋白组学技术筛选精神分裂症患者血清蛋白标志物,并初步探讨其用于精神分裂症诊断的价值。方法利用表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术及弱阳离子交换表面(CM10)蛋白芯片检测66例精神分裂症患者和62名正常对照血清蛋白质谱。将患者和对照随机分为训练集(30例患者30名对照)和验证集(36例患者和32名对照),前者用于筛选精神分裂症差异蛋白标志物并建立人工神经网络(ANN)诊断模型,后者用于模型诊断效度的盲法验证。结果精神分裂症与正常对照血清蛋白质谱图有15个明显表达差异的蛋白质峰(P<0.001),筛选其中质荷比(m/z)分别为2820、3219、3317、4284和4347的5个蛋白质峰作为标志蛋白(P<10-4)建立人工神经网络诊断模型。利用该模型对精神分裂症进行盲法预测,结果表明其对精神分裂症的诊断灵敏度和特异度分别为91.7%和93.8%。结论精神分裂症患者较正常人血清具有差异表达的特征蛋白,可能对其诊断有参考价值。

Objective To identify serum protein markers for diagnosis of schizophrenia using surface-enhanced laser desorption-ionization time of flight mass spectrometry （SELD1-TOF-MS） and CM10 chip. Methods 66 patients with schizophrenia and 62 normal controls were included. Sample were randomly assigned into two subsets, the training set （ n = 60, 30 in each）, and the testing set （n = 68, 36 patients with schizophrenia and 32 normal controls）. The training set was used for identifying the statistically significant peaks as well as for developing artificial neural network （ANN） model. And the testing set was used for blind test to validate the diagnostic efficiency of ANN model. The SELDI-TOF-MS and CM10 protein chips were performed to screen for differentially expressed proteins in serum from patients and mormal controls. Restilts Total 15 differentially expressed proteins between patients and controls were identified. Among them, five proteins （P 〈 10-4, m/z at 2820, 3219, 3317, 4284 and 4347） were chosen to develop ANA based diagnostic model. The model was blindly tested with the testing set for diagnosing schizophrenia. The sensitivity and specificity was 91.7% and 93.8% , respectively. Conclusions The preliminary results suggested that patients with schizophrenia may have specific serum protein expression different from normal controls. These biomarkers may have the potential in diagnosis of schizophrenia.