结肠癌与大肠腺瘤及癌旁正常肠黏膜组织差异表达蛋白的筛选

Proteomic analysis of expressed differentially proteins involved in human colorectal carcinomas , colorectal adenoma and normal colonic mucosa tissues

目的:探讨结肠癌、大肠腺瘤及正常肠黏膜组织中蛋白质组的表达差异及其意义。方法:应用表面增强激光解析离子化飞行时间质谱(SELDI-TOF-MS)技术检测结肠癌、大肠腺瘤及正常肠黏膜组织的蛋白图谱,通过BiomarkerWizard软件分析发现差异蛋白,用蛋白质组学数据库检索出部分差异蛋白。结果:发现16种差异蛋白,其中大肠癌组织质荷比(M/Z)为4 904、7 602、7 705、14 990和15 708的蛋白峰强度显著高于正常组织和大肠腺瘤患者,P<0.01;大肠腺瘤与正常人相比,除在M/Z为4 904的蛋白峰强度差异有统计学意义外(P=0.006),其余差异均无统计学意义,P>0.05;数据库检索结果提示,这些蛋白分别为CEA、p53R2、HCG2020031、Kallikrein-11(hk11)和CD99,其中,CEA为目前临床上常用的肿瘤标志,另外4种差异蛋白质可能具有成为肿瘤新标志潜能。结论:SELDI-TOF-MS技术能很好的显示结肠癌、大肠腺瘤与正常肠黏膜组织间的差异表达蛋白,本研究筛选出的其他4种新差异表达蛋白质有可能为研究结肠癌癌变过程中的生物学行为提供新的分子标志。

OBJECTIVE：To study the differentially expressed proteins in eolorectal carcinoma tissues,colorectal adenoma tissues and the normal colonic mucosa by proteomics techniques. METHODS： Tissue samples from colorectal carcinoma patients,colorectal adenoma patients and healthy controls were analyzed by SELDI-TOF-MS using WCX magnetic heads（MB-WCX）. The resulting SELDI-TOF-MS spectral data were analyzed using the Biomarker Wizard to find differential proteins. The differential proteins were identified by searching the Swiss-Prot and TrEMBL. RESULTS： A total of 16 mass peaks were identified. The levels of five peaks at mass： charge ratios（m/z） of 4 904,7 602,7 705,14 990 and 15 708 were significantly higher in the patients with colorectal carcinoma than that in patients with colorectal adenoma and heahhy controls（P〈0.01）; Compared with healthy controls,the level of peaks at mass=charge ratios（m/z） of 4 904 in patienls with colorectal adenoma was statistically significant （P=0. 006） ,while the others were not（P〉0.05）. Database search revealed that the five peaks corresponded to CEA, p53 R2, HCG2020031, Kallikrein- 11 （ hk11 ） and CD99 respective ly. （hher four kinds of differential proteins might had the potential as new tumor markers besides CEA. CONCLUSIONS= Proteomic analysis can identify the proteins with variance among colorectal carcinoma,colorectal adenoma tissues and normal co Ionic mucosa as well as providing possiable new biomarkers correlated with biological behavior of colorectal carcinoma.