摘要
目的探讨表面增强激光解析离子化飞行时间质谱(SELDI-TOF-MS)技术在筛选神经管缺陷胎儿母亲尿液中蛋白质标志物的应用。方法经超声确诊为神经管缺陷胎儿的孕妇20例和正常孕妇15例。神经管缺陷包括脊柱裂10例,无脑儿5例,脑积水5例。所有孕妇均取清晨空腹尿5ml,离心后取上清,选用CM10芯片检测。采用PBSⅡC型蛋白质芯片阅读机读取数据。设定优化相对分子质量范围1000～30000Da。数据分析使用Ciphergen protein chip 3.1.1软件。结果共检测到39个尿液差异蛋白质峰,有统计学意义的差异蛋白质峰5个。病例组中有4种蛋白质高表达,相对分子质量分别为8320,8209,9099,10567;1种蛋白质低表达,相对分子质量3458。建立决策分类树,得到带有3个终结点的决策分类树,获得2个标志性蛋白质,分子量为9096,8244。进行留一法交叉验证后,神经管缺陷诊断模型的灵敏度为80.0%,特异度为93.3%。结论应用SELDI-TOF-MS技术可以在孕妇尿液中筛查出神经管缺陷的特异性蛋白质标志物,进一步可用于神经管缺陷产前早期无创诊断。
Objective Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF-MS） to detect the specific protein biomarkers of maternal urine of the fetus with neural tube defects（NTDs）. Methods Of the 35 maternal urine samples ob- tained, 20 were from patients whose fetus were NTDs and 15 were from healthy volunteers undergoing pregnancy routine μltrasonography examination. 10 spina bifida, 5 anencephaly and 5 hydrencephaly were included in NTDs. All fasting urine samples about 5ml were obtained early in the morning and then the urine samples were centrifugated. Proteinchip reader PBS Ⅱ C and CM10 chip （Ciphergen Biosystems） were utilized. The optimal detection mass / charge size（m/z） range was between 1000 and 30 000 Da. The data was analyzed by ProteinChip Software （version 3.1.1; Ciphergen Biosystems）. Results A total of 39 qualified mass peaks （signal-to-noise ratio〉5）were detected in NTDs and control group . Compared with the spectra of control group, there were 5 potential biomarkers detected in the spectra of NTDs group. The protein expression was high in 4 of 5（m/z 8 320,8 209,9 099, 10 567）and low in the 1 of 5（m/z 3 458）. The Biomarker Pat- tern Software automatically, under given conditions, selected 2 biomarker proteins （m/z 9 096,8 244）to be used to establish a three layer decision tree to differentiate NTDs from control. The sensitivity and specificity of decision tree was 80.0% and 93.3%,respectively. Conclusion The screening on specific urine protein biomarkers of NTDs can be performed by SELDI-TOF-MS, and it may be used for the early pregnancy diagnosis with NTDs.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2009年第3期220-224,共5页
Journal of China Medical University
基金
国家自然科学基金资助项目(30571934)
关键词
神经管缺陷
表面增强激光解析离子化飞行时间质谱
产前诊断
蛋白质标志物
neural tube defects
surface-enhanced laser desorption/ionization rime-of-flight mass spectrometry
pregnancy diagnosis
protein biomarker
