摘要
目的:研究正常大鼠的结直肠黏膜从结直肠腺瘤发展至结直肠腺癌,最终演变为结直肠癌肝转移的发病过程中,各个阶段黏膜或肿瘤组织的差异表达蛋白,从中发现有助于结直肠癌早期诊断的标志物,并进一步探求结直肠癌的发病机制。方法:给予90只雄性Wistar大鼠腹腔注射1,2-二甲肼(1,2-dimethylhydrazine,1,2-DMH),于不同周数时处死大鼠,将获取的标本分为正常黏膜组、腺瘤组、腺癌组和肝转移组;分别留取各个阶段的组织标本,提取蛋白质,行二维凝胶电泳后,选取表达有显著差异的点进行质谱检验和生物信息学分析。结果:通过二维凝胶电泳图和质谱分析,最终鉴定出10个差异表达蛋白,包括α-烯醇化酶(α-enolase)、心脏α-肌动蛋白(cardiac α-actin,CA)、transgelin蛋白、肌球蛋白调节轻链(myosin regulatory light chain,MRLC)-平滑肌型、3-磷酸甘油醛脱氢酶(glyceraldehyde-3-phosphate dehydrogenase,GAPDH)、结合珠蛋白(haptoglo-bin)、二硫键异构酶(disulfide isomerase,DI)、线粒体肌酸激酶(creatine kinase,mitochondrial,CK-m)、热休克蛋白8(heat shock protein-8,HSP-8)和角蛋白复合体2(keratin complex-2,KC-2)。结论:在由1,2-二甲肼诱导发生的大鼠结直肠癌肝转移的各个发病阶段的黏膜或肿瘤组织间,存在差异表达蛋白,这些蛋白可能成为结直肠癌早期诊断的候选生物标志物。蛋白质组学技术是一种可用于初步筛选生物标志物的有效方法。
Objective：To research the proteins differentially expressed during evolution of experimental colorectal carcinoma （normal mucosa→adenoma→carcinoma→liver metastasis） so as to find the early diagnostic biomarker of colorectal cancer as well as to understand its pathogenesis mechanism. Methods： Ninety male rats were injected with 1,2-dimethylhydrazine intraperitoneally and sacrificed at different weeks to establish the experimental colorectal tumor models （from normal mucosa to liver metastasis）. These sam- ples at different stages were collected and divided into four groups （ normal mucosa group, adenoma group, carcinoma group, and liver metastasis group）. The proteins of these 4 groups were extracted to conduct 2-dimensional gel electrophoresis. The differential protein spots were examined by mass spectrometry and analyzed by bioinformatics. Results：Ten differentially expressed proteins were identified by 2-dimensional gel electrophoresis and mass spectrometry including et-enolase, cardiac α-actin （CA）, transgelin protein, myosin regulatory light chain smooth muscle isoform （MRLC）, glyceraldehydes-3-phosphate dehydrogenase （GAPDH）, haptoglobin, disulfideisomerase （DI） , creatine kinase mitochondrial （CKm） , heat shock protein-8 （HSP-8） and Keratin complex-2 （KC-2）. Conclusions： There exist differentially expressed proteins at various stages during the evolution of colorectal carcinoma. These proteins may be the candidate biomarkers for the early diagnosis of colorectal carcinoma. Proteomic technology is an effective way for preliminary identification of the tumor biomarkers.
出处
《肿瘤》
CAS
CSCD
北大核心
2008年第12期1023-1028,共6页
Tumor
关键词
结直肠肿瘤
蛋白质组学
电泳
凝胶
双向
动物
实验
Colorectal neoplasms
Proteomics
Electrophoresis, gel, two-dimensional
Animal, laboratary
