表面增强拉曼光谱在胃癌诊断和分期中的应用  

Application of surface-enhanced Raman spectroscopy in diagnosis and staging of gastric cancer

作　　者：刘燕玲 黄丽韫[1] 钟会清 卢敏[1] 侯雨晴 毛华[1] Yan-Ling Liu;Li-Yun Huang;Hui-Qing Zhong;Min Lu;Yu-Qing Hou;Hua Mao(Department of Gastroenterology, Zhujiang Hospital, Southern Medical University Guangzhou 510282, Guangdong Province, China;SATCM Third Grade Laboratory of Chinese Medicine and Photonics Technology, College of Biophotonics, South China Normal University, Guangzhou 510631, Guangdong Province, Chin)

机构地区：[1]南方医科大学珠江医院消化内科,广东省广州市510282 [2]华南师范大学生物光子学研究院国家中医药管理局中医药与光子技术三级实验室,广东省广州市510631

出　　处：《世界华人消化杂志》2018年第18期1102-1110,共9页World Chinese Journal of Digestology

基　　金：广州市科技计划项目;No.201604020168~~

摘　　要：目的探讨表面增强拉曼光谱技术(surface-enhanced Raman spectroscopy,SERS)在胃癌(gastric cancer,GC)诊断中的应用价值,并评估SERS在GC分期中的可行性.方法利用In Via+Plus型激光共焦显微拉曼光谱仪检测63例经病理学确诊GC患者,45例GC前病变患者,50例健康志愿者的血清,分析不同血清SERS光谱的特征,采用单因素方差分析(ANOVA)、独立样本t检验、主成分分析(principal component analysis,PCA)、线性判别分析(linear discriminant analysis,L D A)等统计分析方法进行统计学处理,利用受试样品工作特征曲线(receiver operating characteristic curve,ROC)评价诊断效能.结果 GC、GC前病变、正常组血清的平均SERS光谱存在差异,在725、1099、1133、1589/cm位移处,GC组血清SERS强度高于正常组;在1004、1328、1446、1657/cm位移处,GC前病变组和GC组血清SERS强度均弱于正常组.相比正常组和癌前病变组,GC患者血清在815/cm处有特征峰.在1133、1446、1589/cm位移处,GC TNMⅢ-Ⅳ期患者血清SERS强度明显强于Ⅰ-Ⅱ期;在1004/cm位移处,Ⅰ-Ⅱ期血清SERS谱峰强度则明显强于Ⅲ-Ⅳ期.利用PCA-LDA统计方法得到SERS技术诊断GC的灵敏度、特异性和准确率分别为96.8%(61/63),78%(39/50)和88.5%(100/113);ROC曲线下面积为0.927;SERS技术区分GC TNMⅠ-Ⅱ期和Ⅲ-Ⅳ期的灵敏度、特异性和准确率分别为97.5%(39/40),73.9%(17/23)和88.9%(56/63);ROC曲线下面积为0.857.结论基于表面增强拉曼光谱技术对GC、GC前病变及健康人的血清进行检测和分析,可有效鉴别GC、GC前病变及健康人,并且能够对不同分期的GC做出有效区分,有望成为GC的早期诊断、临床决策指导以及预后评估的新方法.AIM To investigate the value of surface-enhanced Raman spectroscopy（SERS） in the diagnosis of gastric cancer（GC） as well as its feasibility in distinguishing GC of different TNM stages. METHODS InV ia laser confocal microscope-Raman spectrometer was used to examine the sera of patients with pathologically confirmed GC（63 cases）, those with gastric precursor lesions（45 cases）, and healthy volunteers（50 cases）. Oneway ANOVA, Student＇s t test, principal component analysis（PCA）, and linear discriminant analysis（LDA） were used to process and analyze the Raman spectral data, and the receiver operating characteristic（ROC） curve analysis was performed to evaluate the diagnostic efficiency. RESULTS The average SERS spectra of sera differed significantly among GC patients, patients with precancerous lesions, and healthy volunteers. The intensity of Raman spectra located at 725, 1099, 1133, and 1589/cm was significantly stronger in GC patients than in normal controls, while the intensity of Raman spectra at 1004, 1328, 1446, and 1657/cm was significantly stronger in normal persons. A strong enhancement in the intensity of the peak at approximately 815/cm was observed in the spectra of the serum of GC patients. At the Raman shift of 1133, 1446, and 1589/cm, Raman intensity for serum samples was significantly stronger in GC patients with TNM stage Ⅲ/Ⅳ disease than in those with stage Ⅰ/Ⅱdisease, while the Raman intensity at the Raman shift of 1004/cm was significantly stronger in patients with stage Ⅰ/Ⅱ disease. The sensitivity, specificity, and accuracy of SERS combined with multivariate PCALDA in diagnosing GC were 96.8%（61/63）, 78%（39/50）, and 88.5%（100/113）, respectively, and the area under the ROC curve was 0.927. The sensitivity, specificity, and accuracy of SERS combined with multivariate PCALDA in distinguishing TNM stage Ⅰ/Ⅱ GC and stage Ⅲ/Ⅳ disease were 97.5%（39/40）, 73.9%（17/23）, and 88.9%（56/63）, respectively, and the area under the ROC

关 键 词：表面增强拉曼光谱 胃癌 血清 诊断 分期 

分 类 号：R735.2[医药卫生—肿瘤]