特发性血小板减少性紫癜患儿血清生物标志物的蛋白质组学研究  

Study on proteomics of the serum biomarker from children with ITP.

作　　者：刘春艳[1] 陈红英[1] 刘文君[1] 

机构地区：[1]泸州医学院附属医院儿科,四川泸州646000

出　　处：《中国实用儿科杂志》2009年第10期776-781,共6页Chinese Journal of Practical Pediatrics

摘　　要：目的筛选可用于特发性血小板减少性紫癜(ITP)早期诊断及分型、病情变化监测及判断预后的血清蛋白质标志物,建立ITP诊断模型,验证在血清蛋白质组水平创立ITP的分子诊断新方法。方法所有病例均来自2007年7月至2008年4月泸州医学院附属医院儿科住院及门诊随访的患儿。应用表面增强激光解吸/离子化飞行时间质谱(SELDI-TOF-MS)检测结合在蛋白质芯片上的血清蛋白质,获得25例急性特发性血小板减少性紫癜(AITP)、10例慢性血小板减少性紫癜(CITP)、25例正常对照者血清蛋白表达指纹图谱,并用Biomarker Wizard和Biomarker Paterns System 5.0软件对数据进行分析,建立人工神经网络诊断模型。结果在分子质量与电荷比值(质荷比,mass electronratio,M/E)为2000～20000范围内,ITP组与正常对照组之间差异有统计学意义(P<0.01)的蛋白质峰有31个,其中高表达的蛋白质峰有6个,低表达的蛋白质峰有25个,从分析的结果看最有意义的蛋白质是质荷比为4121.27、5327.56、5890.56的蛋白质,可以看成是ITP的血清生物标志物;AITP组与CITP组间差异有统计学(P<0.01)的蛋白质峰有9个,高表达的蛋白质峰有7个,低表达的蛋白质峰有2个,从分析的结果看最有意义的蛋白质是质荷比为3930.39、6097.56的蛋白质,可以看成是CITP的血清标志物。分别运用其血清标志物进入人工神经网络组合的诊断模型,可将ITP组与正常儿童准确分组,灵敏度为100%,特异度为100%;而对AITP、CITP组的分型诊断模型其敏感度是92.9%,特异度83.3%。结论质荷比为4121.27、5327.56、5890.56的蛋白质组合可能是ITP的血清生物标志物。质荷比为3930.39、6097.56的蛋白质组合可能是CITP的血清生物标志物。SELDI-TOF-MS技术是寻找疾病相关性蛋白质的有效工具。Objective To screen for the serum protein marker used in the early diagnosis, typing, monitoring and pre- diction of prognosis of idiopathic thrombocytopenic purpura （ITP）, and to eatablish ITP diagnostic model, verifying the new way of molecular diagnosis of ITP at the serum protein level. Methods SELDI-TOF-MS was applied to test the se- rum protein combined with the protein chip. Twenty-five cases of acute ITP, 10 cases of chronic ITP, and 25 finger prints of serum protein from the control group were collected. Biomarker Wizard and the software of Biomarker Patterns System 5.0 were applied to analyze the data and a diagnostic model was established. Results Within the range of mass electron ration （m/e） of 2000-20000, when a contrast was made between the ITP group and the control group, 31 pro- tein peaks were statistically significant （P 〈 0.01 ）, 6 peaks of which were of high expression and 25 low expression. The most significant protein was that with the M/E of 4121.27 5327.56 5890.56, which could be recognized as serum bio- marker for ITP. Nine protein peaks were found statistically significant （P 〈 0.01 ） between the ITP group and the control group, 7 of which were of high expression and 2 low expression. The most significant protein was that with the M/E of 3930.39 6097.56, which could be recognized as serum biomarker for chronic ITP. By integrating respective serum bio- marker from the two types of protein into the diagnostic model of artificial neural network, the ITP group and the control group could be divided accurately with the sensitivity of 100%, specificity of 100%, and the integration＇s sensi- tivity to the diagnostic model of acute and chronic ITP was 92.9%, specificity 83.3%. Conclusions 1 ） There is a significant difference between the levels of serum protein from the ITP group and those from normal children. 2）There is a significant difference between the levels of serum pro- tein from the group of acute ITP and those from chronic ITP group. 3 ）The diagnostic model

关 键 词：特发性血小板减少性紫癜 表面增强激光解刚离子化飞行时间质谱 蛋白质组学 生物标志物 人工神经网络 

分 类 号：R72[医药卫生—儿科]