SELDI-TOF-MS技术筛选鼻咽癌血清肿瘤标志物

Detection of Serum Protein Biomarkers by Surface Enhancedlaser Desorption Ionization Time of Flight Mass Spectrometry in Patients of Nasopharyngeal Carcinoma

目的筛选鼻咽癌患者血清蛋白差异表达并建立诊断模型,分析不同临床特征患者的血清蛋白质谱差异。方法应用SELDI技术分析102例鼻咽癌患者及118例健康对照的血清样本,Bio-marker Wizard和Biomarker Pattern软件分析两组之间的差异,建立分类树诊断模型并进行盲筛验证;进一步分析鼻咽癌不同临床分型及EB病毒感染状态对患者血清蛋白质表达谱的影响。结果发现鼻咽癌与健康对照之间有25个血清蛋白质谱峰差异有统计学意义(P<0.01),13个蛋白峰表达下调,12个蛋白峰表达上调。经Biomarker Pattern软件建立分类树模型,盲法验证其敏感度为97.56%,特异性为88.89%,准确率达92.63%;上行型和下行型鼻咽癌之间发现M/Z为10286Da、7569Da及8149Da的3个血清蛋白质峰差异有统计学意义(P<0.05);EB阳性和EB阴性鼻咽癌间M/Z为9354Da及4596Da的2个血清蛋白质峰差异有统计学意义(P<0.05)。结论 SELDI-TOF-MS技术可筛选出鼻咽癌差异性蛋白并建立鼻咽癌诊断的分类树模型,有望成为鼻咽癌早期诊断的辅助指标;并且用SEDLI技术可以发现一些与鼻咽癌临床特征相关的血清蛋白差异峰。

Objective To analyze the characteristic of serum proteins in nasopharyngeal carcinoma（NPC） patients and establish serum markers pattern for the diagnosis of NPC.Methods Surface enhanced laser desorption ionization time of flight mass spectormetry（SELDI-TOF-MS） technology was applied to analyze serum samples including 102 cases of NPC patients and118 cases of healthy controls.Biomarker Pattern Software（BPS） was used to detect the protein peaks significantly different between NPC patients and healthy controls,then a diagnostic pattern was established.This pattern was further valuated by a blind test.This technology was used to analyze the differential expression of serum proteins mass spectra in patients grouped by clinical classification and EB virus infection.Results Twenty-five significantly different protein peaks were found in serum samples between NPC patients and healthy controls including twelve up-regulated protein peaks and thirteen down-regulated protein peaks.Using BPS,a diagnostic pattern was established.A blind test generated a sensitivity of 97.56%,specificity of 88.89% and accuracy of 92.63% respectively.M/Z values of 10286Da,7569Da and 8149Da were significantly different between ascending type and descending type of NPC（P0.05）;M/Z value of 9354Da and 4596Da were significantly different between EB negative and EB positive respectively（P0.05）.Conclusion SELDI-TOF-MS technology can identify the significantly different protein peaks and establish a diagnostic pattern with high sensitivity and specificity.It will provide a highly accurate approach for the diagnosis of NPC,and SELDI could be used to discover some characteristic of serum proteins relates to different clinical features.