非小细胞肺癌血清蛋白质标志物的检测及鉴定

Detection and identification of specific serum protein markers of non-small cell lung cancer

目的运用蛋白组学技术检测非小细胞肺癌（NSCLC）特异性的血清蛋白标志物，并验证联合应用标志物对非小细胞肺癌的检出效能。方法运用表面增强激光解吸电离飞行时间质谱（SELDI—TOF-MS）等蛋白组学技术对112例非小细胞肺癌患者和123例对照者血清的蛋白质谱进行分析检测，并对差异性峰值进行鉴定，随后运用蛋白质抗体芯片对检测出的特异性蛋白质标志物进行验证，并衡量标志物的联合检出效能。结果质荷比峰值为6628、9191、11412的3个蛋白质构建了具有高区别能力的非小细胞肺癌判别模型。质荷比为6628的蛋白鉴定为载脂蛋白C-I，在非小细胞肺癌血清中下调；质荷比为9191和11412的蛋白分别鉴定为触珠蛋白α-1链和S100A4蛋白，在非小细胞肺癌血清中上调。三者的联合应用在盲法检测组中的敏感性和特异性分别为96．56％和94．79％。结论载脂蛋白C-I、触珠蛋白α1链和-S100A4蛋白作为非小细胞肺癌特异性的血清蛋白质标志物，可以用于非小细胞肺癌的早期诊断。

Objective To detect the specific serum protein biomarkers for non-small cell lung cancer （NSCLC） by using proteomics techniques, and verify their detection efficacy for NSCLC. Methods Serum proteomie profiles of 112 eases of NSCLC and 123 controls were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy （SELDI-TOF-MS） , and the candidate protein biomarkers were identified by a series of proteomic methods and validated by ProteinChip immunoassays. Finally, the efficacy of these protein biomarkers for the detection of NSCLC was verified. Results These proteins with m/z of 6628,9191,11 412 could discriminated NSCLC from non-cancer controls with high de- tectable ability. The protein biomarker with m/z of 6628 was down-regulated in NSCLC patients and identi- fied as apolipoprotein C-I, and the other two biomarkers with m/z of 9191 and 11 412 were up-regulated and identified as haptoglobin alpha-1 chain and SI00A4, respectively. The sensitivity and specificity of this detective model were 96. 56% and 94. 79% respectively in the blind testing set. Conclusion Apolipopro- tein C-I, haptoglobin alpha-1 chain and S100A4 could be used for the early diagnosis of NSCLC as specific serum protein biomarkers.