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目的运用液体蛋白芯片飞行时间质谱(MALDI-TOF-MS)技术分析19片段角蛋白(CYFRA21-1)阴性的肺鳞癌血清蛋白质表达谱,筛选具有诊断意义的血清标志物,用于CYFRA21-1阴性的肺鳞癌的早期诊断.方法采集60例CYFRA21-1阴性肺鳞癌患者和60名正常对照者血清标本,随机分为模型构建组和模型验证组;运用Clinprot磁珠纯化、MALDI-TOF-MS技术及ClinProTools软件检测分析模型构建组血清蛋白表达谱,筛选差异蛋白并建立诊断模型,再用模型验证组标本进行验证.结果模型构建组CYFRA21-1阴性的肺鳞癌患者与正常对照者的血清蛋白质图谱比较,发现差异蛋白23个,筛选出质荷比为3883.83(m/z)、4640.68(m/z)、6629.27(m/z)、7763.29(m/z)、9284.66(m/z)的蛋白建立诊断模型,模型敏感性为90.0%,特异性为96.7%,其中差异蛋白6629.27(m/z)为肿瘤高表达,差异蛋白3883.83(m/z)、4640.68(m/z)、7763.29(m/z)、9284.66(m/z)为肿瘤低表达.结论运用MALDI-TOF-MS技术可筛选出CYFRA21-1阴性的肺鳞癌血清中的特异性标志物,为肺鳞癌的早期诊断提供了新的检测方法.“,”Objective To establish proteomic profiling using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS) and to seek biomarkers of CYFRA21-1 negative human lung squamous for early diagnosis.Methods The serum samples of 60 CYFRA21-1 negative human lung squamous carcinoma patients and 60 normal control subjects were randomly divided into two groups to build up the group of establishing model and the group of verifying model.The serum samples of establishing model were analyzed by the technique of MALDI-TOF-MS and ClinProTools software to screen the differential proteins and establish the diagnostic model.The differential proteins and the model were verified by the groups of verifying model. The interested proteins were identified.Results The serum protein spectrums in the group of establishing model including CYFRA21-1 negative human lung squamous carcinoma patients and normal control subjects were compared and got 23 differential proteins.The model was established and the sensitivity and specificity was 90.0%and 96.7% respectively.The up-regulated proteins were 6629.27(m/z);The down-regulated protein was 3883.83(m/z),4640.68(m/z),7763.29(m/z) and 9284.66(m/z).Conclusion The biological markers in the earlier period of CYFRA21-1 negative human lung squamous carcinoma can be detected by the technology of MALDI-TOF-MS and the software of ClinProTools.It could be a new,convenient analyzing method in the early diagnosis and therapy of human lung squamous carcinoma.