亚健康状态中阳虚质与阴虚质患者血清蛋白质谱诊断模型的建立与评价

Establishment and evaluation of a diagnostic model of serum protein mass spectrometry for Yang-deficiency and Yin-deficiency constitutionin sub-health state

目的应用蛋白质组学技术和生物信息学方法建立并评价亚健康状态中阳虚质与阴虚质患者血清蛋白质谱诊断模型。方法采用弱阳离子交换蛋白芯片CM10和SELDI-TOF-MS技术检测63例血清标本(其中健康对照20例,亚健康阳虚质患者22例、阴虚质患者21例),结合Ciphergen Protein Chip 3.1、Biomarker Wizard 3.2和SPSS 17.0等软件筛选出有显著差异的蛋白质谱峰;采用Biomarker Patterns 5.0对差异蛋白质谱峰分组和建立诊断模型,并选择敏感性、特异性、误诊率、漏诊率、ROC曲线作为指标对该模型进行评价。结果获得317个可识别的血清蛋白差异质谱峰,含量差异具有显著性(P<0.01)的蛋白有23个,从中筛选出1370.09、1051.31、1164.23、1195.28、1088.50、1117.98、1094.24七个血清蛋白质谱峰建立亚健康状态阳虚质、阴虚质疾病诊断模型,该模型对阳虚质的敏感性为86.36%、特异性为85.37%、ROC曲线下面积为0.969,对阴虚质的敏感性为90.48%、特异性为83.33%、ROC曲线下面积为0.955。结论与健康对照比较,亚健康状态阳虚质和阴虚质患者血清中存在多种异常表达的蛋白质;由1370.09、1051.31、1164.23、1195.28、1088.50、1117.98、1094.24七个血清蛋白质谱峰构建的诊断模型可以较好地诊断亚健康状态阳虚质和阴虚质,具有较高的敏感性与特异性。

Objective TO establish and evaluate a diagnostic model of serum protein mass spectrometry for Yang-deficiency and Yin-deficiency constitution in sub-health state through proteomics and bioinformatics methods. Methods CM10 Protein Chip and SELDI-TOF-MS were used to detect the serum proteomic patterns of 22 cases of Yang-deficiency constitution and 21 cases of Yin-deficiency constitution in sub-health state,20 healthy control subjects. The data were analyzed by Ciphergen Protein Chip 3. 1,Biomarker Wizard 3. 2 and SPSS 17. 0 software. Furthermore,the establishment and evaluation of a diagnostic modelwere executed by Biomarker Patterns 5. 0. Results 317 identifiable differential proteins peaks were obtained,including 23 protein peaks with significant difference（ P 0. 01）. Seven mass spectrum peaks such as 1370. 09,1051. 31,1164. 23,1195. 28,1088. 50,1117. 98 and 1094. 24 were used to establish the diagnostic model. The sensitivity,specificity and area under the ROC curve of the model were86. 36%,85. 37% and 0. 969 respectively for the diagnosis of Yang-deficiency constitution,and 90.48%,83. 33%,0. 955 for Yin-deficiency constitutionin sub-health state. Conclusion There are many kinds of abnormal expressed serum proteins in sub-health patients with Yang-deficiency and Yin-deficiency constitution,compared with the healthy control. The diagnostic model established by mass spectrum peak of 1370. 09,1051. 31,1164. 23,1195. 28,1088. 50,1117. 98 and 1094. 24 can be used to diagnose Yang-deficiency and Yin-deficiency constitution in sub-health state,with high sensitivity and specificity.