特发性血小板减少性紫癜血小板差异蛋白质组诊断模型的实验研究

Diagnosis Model of Idiopathic Thrombocytopenic Purpura based on Platelet Differential Proteome

本研究旨在建立一种简便快速、灵敏度高、特异性好的特发性血小板减少性紫癜(ITP)的实验诊断方法。应用表面增强激光解析电离飞行时间质谱技术(SELDI-TOF-MS)检测60例ITP、60例白血病、60例再生障碍贫血及60例健康成人血小板裂解液,各疾病组及正常组均随机分为训练集(120例)和验证集(120例),筛选出有明显表达差异的标志蛋白,利用人工神经网络建立ITP诊断模型,并用SPSS 17.0进行盲法验证。结果表明,m/z为2234.30、3476.36、7526.29的蛋白在ITP患者高表达,m/z为4990.02、5152.39的蛋白低表达。诊断模型的灵敏度和特异度分别为80.6%和77.3%,盲法验证工作特征曲线下面积为0.837。结论:基于血小板蛋白质谱图建立的人工神经网络诊断模型对ITP的临床诊断和分子病理研究具有重要的参考价值。

This study was purposed to establish a new quick and simple diagnostic method with high sensitivity and good specificity for idiopathic thrombocytopenic purpura （ITP） and to evaluate its significance. 240 platelet lysates （ from patients with ITP, leukemia, MDS, and healthy adults, each of 60 cases） were randomly assigned to training set （120 cases ）or validation set（ 120 cases）, all of them were detected by surface enhanced laser desorption ionization time of flight mass spectrometry （SELDI-TOF-MS）, in ovder to identify the differentially expressed protein, the diagnostic model was established by means of artificial neural network （ ANN）, and was validated by blind test with SPSS 17.0. Ths results showed that 5 marked proteins significantly differentially expressed （ P 〈 0.01 ）, m/z of highly expressed proteins were 2234.30,3476.36, and 7526.29, m/z of low expressed proteins were 4990.02 and 5152.39, respectively. The sensitivity and specificity of diagnostic model were 80.6% and 77.3% respectively. The area under the ROC curve consisting of the output value of artificial neural network was 0. 837. Efficacy of the model was validated by means of blinded test. It is concluded that the ANN model is useful for clinical diagnosis of ITP on the basis of platelet protein fingerprint spectrum.