血清低相对分子质量差异蛋白质组在食管癌诊断和分期中的作用

Detection of differentially expressed low molecular weight serum proteins for diagnosis and staging of esophageal cancer

目的:研究食管癌癌变过程中血清低相对分子质量蛋白的细微变化,探索食管癌发生的机制,寻找食管癌早期诊断的生物标志物和方法.方法:应用表面激光解析电离飞行时间质谱技术对食管癌患者血清和健康对照血清进行蛋白质谱指纹图谱检测,通过Biomarker Wizard软件筛选差异蛋白,使用人工神经网络软件建立食管癌早期诊断模型并用盲法验证其诊断效果;将食管癌早期和中晚期食管癌患者血清质谱图进行比对分析,寻找各期差异蛋白,并建立分期诊断模型.结果:发现食管癌和正常人差异蛋白5种,早期食管癌和中晚期食管癌差异蛋白3种.通过早期食管癌组和健康对照组建立早期诊断模型的灵敏度87.88%,特异度91.43%,准确度89.71%,经过盲法验证结果为灵敏度95.83%,特异度89.13%,准确度91.43%.早期食管癌和中晚期筛选的差异蛋白建立的分期诊断模型灵敏度75.76%,特异度79.17%,准确度77.19%.结论:表面增强激光解析离子化飞行时间质谱联合人工神经网络技术操作较为简便,在食管癌的诊断和分期上具有可行性.

AIM：To find biomarkers for early diagnosis of esophageal cancer（EC） by detecting differentially expressed low molecular weight serum proteins using mass spectrometry.METHODS：The serum proteomic patterns of EC patients and healthy controls were detected using the surface-enhanced laser desorption/ionization-time of flight-mass spectrometry（SELDITOF-MS）.Differential protein peaks between EC patients and controls were analyzed using the Biomarker Pattern Software,and a model for early diagnosis of EC was developed and validated using an artificial neural network（ANN）.Differential protein peaks between early and advanced EC patients were analyzed to establish a model for staging of EC.RESULTS：Five differential serum proteins were identified between EC patients and controls,and three differential serum proteins were found between early and advanced EC.The diagnostic model established based on the five differential serum proteins between EC patients and controls had a sensitivity of 87.88%,a specificity of 91.43%,and an accuracy of 89.71%.The blind test generated a sensitivity of 95.83%,a specificity of 89.13%,and an accuracy of 91.43%.The staging model established based on the three differential serum proteins between early and advanced EC had a sensitivity of 75.76%,a specificity of 79.17%,and an accuracy of 77.19%.CONCLUSION：SELDI-TOF-MS in combination with ANN is simple and feasible for the diagnosis and staging of EC.