表面增强激光解吸电离-飞行时间质谱在甲状腺癌诊断及临床分期中的应用

Application of SELDI-TOF-MS technology analyzing serum protein profiling in diagnosis of thyroid cancer

目的:用表面增强激光解吸电离-飞行时间质谱(SELDI-TOF-MS)分析正常人和甲状腺癌患者血清蛋白指纹图谱的变化,建立能鉴别正常人和甲状腺癌及Ⅰ-Ⅱ期甲状腺癌和Ⅲ-Ⅳ期甲状腺癌患者的诊断模型。方法:应用SELDI-TOF-MS技术检测72例血清标本的蛋白质质谱,其中甲状腺癌40例(Ⅰ-Ⅱ期26例,Ⅲ-Ⅳ期14例),正常人32例。应用支持向量机和判别分析的方法分析质谱数据,建立甲状腺癌诊断模型并留一法交叉验证。结果:区分甲状腺癌和正常人的诊断模型交叉检验敏感性为100%,特异性为86%,总的符合率为93%;区分Ⅰ-Ⅱ期甲状腺癌和Ⅲ-Ⅳ期甲状腺癌患者的诊断模型对Ⅰ-Ⅱ期甲状腺癌检出的敏感性为77%,特异性为86%,对Ⅲ-Ⅳ期甲状腺癌检出的敏感性为86%,特异性为77%,总的符合率为80%。结论:应用SELDI-TOF-MS技术平台和生物信息技术建立的诊断模型为甲状腺癌的早期诊断及临床分期提供了新的手段。

Aim： To analyze the spectrometric serum protein profiling of patients with thyroid carcinoma and healthy control by surface enhanced laser desorption/ionization time of flight mass spectrometry （SELDI-TOF-MS） , and to establish serum marker pattern for the diagnosis of thyroid carcinoma. Methods：A total of 72 serum samples were detected by SELDI-TOF-MS, including 40 thyroid cancer patients（grade Ⅰ -Ⅱ 26 cases, grade Ⅲ-Ⅳ 14 cases） and 32 cases of healthy control. The data of spectra were analyzed by bioinformatics tools like support vector machine （SVM） and discriminate analysis to establish diagnostic model. Results： The detective model combined with 3 biomarkers could differentiate thyroid cancer from healthy individuals with specificity of 86% ,sensitivity of 100% ,and the total accuracy was 93% ; the detective model combined with 4 biomarkers could differentiate grade Ⅰ - Ⅱ thyroid cancer from grade Ⅲ-Ⅳ thyroid cancer with specificity of 86% , sensitivity of 77% ,at the same time the model could differentiate grade Ⅲ-Ⅳ thyroid cancer from grade Ⅰ - Ⅱ thyroid cancer with specificity of 77% ,sensitivity of 86% , and the total accuracy was 80%. Conclusion： The SELDI- TOF-MS protein chip and bioinformation technology based on analytical method using the peripheral blood sample is a new approach for the clinical diagnosis of thyroid carcinoma.