WCX纳米磁珠在肝细胞癌血清蛋白质组中的应用及其临床意义

Application of WCX Magnetic Bead for Serum Proteome Profiling in Hepatocellular Carcinoma and Its Clinical Significance

目的:探讨蛋白指纹图谱技术筛选肝细胞癌(HCC)患者血清中可用于诊断的特异性标志物。方法:采用弱阳离子纳米磁性微球捕获血清中的蛋白,ProteinChip PBS II-C型蛋白质芯片阅读仪检测绘制成蛋白指纹图谱。所有蛋白指纹图谱采用Biomarker Wizard 3.1分析之后用Biomarker Patterns Software识别最终用于诊断的蛋白标志物并优化组合建立诊断模型。结果:在肝细胞癌患者和对照组之间找到72个差异蛋白峰(P<0.01)。其中质荷比(m/z)为4471、8936、11670和13752的蛋白峰建立肝细胞癌的诊断模型。该诊断模型能很好地把肝细胞癌患者从正常人群中区分出来,其敏感性为93.3%(56/60),特异性为95.1%(78/82)。经双盲实验验证,该模型对肝细胞癌诊断的敏感性为88.9%(32/36),特异性为90.6%(58/64)。结论:采用纳米磁性微球与蛋白质芯片阅读仪联用的蛋白指纹图谱技术可以检测肝细胞癌患者血清中的特异性蛋白标志物,并建立敏感性和特异性均较高的肝细胞癌诊断模型。

Objective： To screen for the potential protein biomarkers in serum for the diagnosis of hepatocellular carcinoma（HCC） using proteomic fingerprint technology.Methods： Proteomic fingerprint technology combining magnetic beads with MALDI-TOF-MS was used to profile and compare the serum proteins from 96 patients with HCC and 146 healthy blood donors.Proteomic patterns associated with HCC were identified by Biomarker Patterns Software.Model of biomarkers was constructed and evaluated using the Biomarker Patterns Software.Results： A total of 72 discriminating m/z peaks were identified that were related to HCC（P〈0.01）.The model of biomarkers constructed by the Biomarker Patterns Software based on the four biomarkers（4471,8936,11670,13752） generated excellent separation between the HCC and control groups.The sensitivity was 93.3%（56/60） and the specificity was 95.1%（78/82）.Blind test data indicated a sensitivity of 88.9%（32/36） and a specificity of 90.6%（58/64）.Conclusion： Biomarkers for HCC can be discovered in serum by MALDI-TOF-MS combining the use of magnetic beads.The pattern of combined markers provides a powerful and reliable diagnostic method for HCC with a high sensitivity and specificity.