基于支持向量机的大肠黏液腺癌术前血清蛋白质标志物检测及分析

Biomarker Discovery of Colorectal Mucinous Adenocarcinoma by Fingerprint and Support Vector Machine

应用表面加强激光解吸电离-飞行时间质谱(SELDI-TOF-MS)技术和CM10蛋白质芯片从大肠黏液腺癌和非黏液腺癌患者中成功地筛选出了大肠黏液腺癌患者血清特异性相关蛋白。应用美国CipherGen公司CM10蛋白质芯片和PBSⅡ型蛋白质芯片阅读仪检测53例大肠癌患者(黏液腺癌12例,非黏液腺癌41例)患者血清蛋白质指纹图谱。采用ZUCI-Protein Chip Data Analyze System分析软件包进行分析,离散小波去噪音,结合支持向量机筛选肿瘤标志物,建立大肠黏液腺癌的术前诊断模型。12例大肠黏液腺癌患者与41例大肠非黏液腺癌患者的血清蛋白质有12个蛋白质峰强度有显著差异。其中质荷比为24297和23434m/z处的蛋白质峰强度统计学P值分别为0.0067和0.0092,差异有极显著统计学意义。支持向量机筛选出24297、3322、3822和4353m/z蛋白质峰作为生物标志物进行检测和预测准确率,其中12例大肠黏液腺癌患者中有10例患者被正确识别,41例大肠癌非黏液腺癌患者中有39例被正确识别,准确率为92.45%(49/53)。该方法可以较好地应用于区别大肠黏液腺癌和非黏液腺癌,进行术前病理鉴别,指导进行大肠黏液腺癌的手术和综合治疗。

To discover special serum protein of colorectal mucinous adenocarcinoma （MA） and nonmucinous adenocarcinoma （nMA） preoperatively by using the technology of surface enhanced laser desorption/ ionization-time of flight-mass spectrometry （SELDI-TOF-MS） and support vector machine. The potential tumor biomarkers in serum from 12 MA patients and 41 nMA patients were screened by the technology of SELDI-TOF- MS and CM10 Protein Chip （CipherGen Company, USA）. The CM10 protein chips was analyzed by PBS II protein chip reader and the protein information was transformed into the form of spectra. The ZUCI-Protein Chip Data Analyze System software package was used to analyze the results. Discrete wavelength analysis was used to eliminate noise and subtract the baseline. A linear support vector machine （SVM） classifier was used to identify peaks. MA was compared with nMA in order to search for proteomic difference between different pathological types. The intensity of 12 proteins in the two groups was significantly different. Among them the P value of the 24 297 and 23 434 m/z were 0.0067 and 0.0092, respectively. The model formed by four protein peaks of 24 297, 3 322, 3 822 and 4 353 m/z was able to distinguish MA from nMA patients with high accuracy. Ten cases in 12 MA patients and 39 cases in 41 nMA patients were classified correctly. The accuracy was 92.45% （49/53）. The specific serum protein in MA patients can be preoperatively diagnosed by SELDI-TOF-MS with high accuracy. This method possesses a potential in clinical application.