蛋白芯片技术筛选肝癌血清标志蛋白的初步研究

Screening of serum biomarkers in hepatocellular carcinoma by SELDI technique:a preliminary study

目的应用表面增强激光解吸电离飞行时间质谱技术(SELDITOFMS)从肝癌患者血清中筛选标志蛋白,找出最佳的标志蛋白组合模式作为临床诊断指标。方法采用WCX2芯片及SELDITOFMS技术对34例肝癌患者及34例健康对照组血清进行蛋白质指纹图谱检测分析,所得到的结果采用BiomarkerWizard和BiomarkerPatternsSystem软件分析。结果发现肝癌患者和健康对照组血清蛋白质指纹图谱之间有17个稳定的标志蛋白,其中有6个标志蛋白在肝癌患者血清中高表达,11个标志蛋白在肝癌患者血清中低表达。分析系统筛选出13752Da及11472Da标志蛋白建立起一个肝癌的诊断模型,对肝癌的诊断特异性为97.06%,敏感度为91.18%,及阳性预测率为96.88%。结论SELDITOFMS技术的特异性及敏感度远远高于目前所采用的某一单独的标志物的血清学诊断,其结果对进一步研究肝癌的蛋白质组学改变及其临床应用可能具有重要意义。

Objective Liver cancer is one of the diseases with higher incidence and mortality. New technologies for the earlier detection of liver cancer are urgently needed. The aim of this study was to screen serum biomarkers in patients with hepatocellular carcinoma by using surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technique.Methods Proteomic spectra were generated by mass spectroscopy in 88 cases, including 34 cases of hepatocellular carcinoma that had been pathologically confirmed with aged 45 to 94 years, and 34 cases of healthy control aged 20 to 78 years. 68 spectra obtained were used to train and develop a decision tree classification algorithm.Results A total of 17 distinguished proteomic peaks were detected, two of which were used to build a proteomic pattern. The results yielded a sensitivity of 91.18% (32/34), specificity of 97.06% (33/34), and positive predictive value of 96.88%.Conclusion SELDI-TOF-MS offers a unique platform for the proteomic detection of hepatocelllular carcinoma. It also offers a noninvasive method to further study the proteomic changes in the development and progression of liver cancer.