高发区食管癌及癌前病变的血清蛋白质谱分析

目的 检测高发区食管癌及癌前病变患者血清蛋白质谱,建立蛋白指纹图谱模型并探究其筛查价值.方法 收集38名健康对照者、63例食管鳞状上皮不典型增生患者(I级26例,Ⅱ级26例,Ⅲ级11例)和36例进展期食管癌患者的内镜活检和血清标本,用CM10蛋白芯片及表面增强激光解析电离飞行时间质谱(SELDI-TOF-MS)技术检测标本的蛋白表达谱.支持向量机算法分别建立食管癌及癌前病变诊断模型,并经留一法交叉验证.结果 ①区分进展期食管癌和健康对照的诊断模型特异性为89.47%,敏感性为83.33%.②区分进展期食管癌和Ⅰ、Ⅱ、Ⅲ级不典型增生的诊断模型的特异性分别为92.31%、80.77%、90.91%,敏感性分别为80.56%、83.33%、94.44%.③在上述诊断模型中,质荷比(m/z)峰值在相对分子质量4291、5644、5664、8775处重复出现.结论 SELDI-TOF-MS技术和支持向量机算法的应用,为高发区高危人群中食管癌及癌前病变的早期筛查和诊断提供了一条新途径.4291、5644、5664、8775 4个质荷比峰对食管各级病变有相似的分类作用,可能是与食管癌变过程中相关的生物学标志物.

Analysis of serum proteomic pattern between patients with esophageal cancer and precancerous lesions in high risk area

Objective To evaluate the potential differences in serum proteomic profiles between patients with esophageal squamous cell carcinoma(ESCC)and precancerous lesions in order to establish proteomic pattern model for diagnosis of ESCC and precancerous lesions in high risk area,and to investigate its value in screening ESCC.Methods The serum and endoscopic biopsy samples were obtained from 38 normal controls,63 patients with atypical hyperplasia(class Ⅰ 26 cases,class Ⅱ 26 cases,class Ⅲ 11 cases)and 36 patients with advanced esophageal carcinoma.The serum proteomic patterns were examined using surface enhanced laser desorption/ionization time of flight mass spectrometry(SELDI-TOF-MS)and CM10 protein chip.The data was analyzed and disease diagnostic models were established using support vector machine(SVM).The diagnostic model was evaluated and validated by leave one cross validation.Results ①The diagnostic model could differentiate advanced esophageal carcinoma from normal controls with a specificity of 89.47%and a sensitivity of 83.33%.②The results delivered 92.31%,80.77% and 90.91%specificity,and 80.56%,83.33%and 94.44%sensitivity for discrimination of atypical hyperplasia Ⅰ,Ⅱand Ⅲ,respectively,using diagnostic models.③Four(4291,5644,5664,8775)m/z peaks observed repeatedly using diagnostic models.Conclusions The SELDI-TOF-MS and SVM provide a new approach for discrimination of ESCC and precancerous lesions in high risk area.Four(4291,5644,5664,8775)m/z peaks may considered as potential biomarkers which related to the ESCC and esophageal precancerous lesions.