结肠癌肿瘤自身抗体谱筛选及其应用  

Screening and Application of Human Colon Carcinoma Auto-antibody Profile

作　　者：冉宇靓[1] 胡海[1] 赵泽国[1] 孙立新[1] 杨治华[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所细胞及分子生物学室,北京100021

出　　处：《肿瘤防治研究》2008年第5期328-331,346,共5页Cancer Research on Prevention and Treatment

基　　金：国家科技攻关计划资助项目(2004BA703B05)

摘　　要：目的本研究拟寻找鉴定结肠癌自身抗体谱,研究这些自身抗体作为结肠癌诊断候选血清标志物的可能性,同时鉴定这些自身抗体的抗原为研究结肠癌发生、发展相关的基因提供线索。方法用结肠癌组织建立了库容量达5×105pfu的cDNA表达文库,用结肠癌患者血清进行了文库血清学分析(SEREX),筛选获得了阳性抗原克隆,进一步分析了其中4个克隆与30例结肠癌和30例正常人血清的反应情况。结果获得的33个阳性克隆中,31个剪切成功,2个克隆与已知EST序列明显无同源性,另外29个克隆与已知基因高度同源。Uracil-DNA glycosylase等4个抗原克隆与结肠癌患者和正常人血清反应阳性率分别为76%(23%)、80%(6%)、77%(0)、73%(66%)。结论本研究发现的29个结肠癌抗原可能参与了结肠癌的发生发展,可能作为结肠癌的治疗潜在分子靶点和结肠癌诊断新的候选血清学标志物。Uracil-DNA glycosylase等3个克隆与结肠癌患者血清的反应阳性率明显高于正常人的血清,其相关自身抗体可作为结肠癌诊断的血清标志物。Objective Screening and identification of the auto-antibody profile of colon cancer may help for identification of serological biomarkers of colon malignancy. Also identification of the auto-antibody related antigens may contribute to the research of genes participating in the colon cancer development. Methods Expression library of colon carcinoma was constructed. The established primary library consisting of 5 × 10^5 clones was screened by autologous serum. 31 positive clones were identified. The nucleotide of cDNA inserts were sequenced and analyzed by BLAST software on EMBL and GenBank. Further more, four positive colons were detected serological immunoreactions with thirty colon cancer serums and thirty normal control serums. Results Of 31 positive clones, tow clones were new antigens without homology to any known genes. The other clones were fragments of known genes which were for the first time defined as antigens of colon cancer. The serological immunoreaction rates of four selected antigens, including Uracil-DNA glycosylase et al, were 76%, 80%, 77% and 73% respectively in colon cancer sera. While the counterpart rates of these amigens in normal sera were 23%, 6%, 0 and 66% respectively. Conclusion Antigens of the positive clones may be frequently involved in the development of colon cancer. The serological reaction rates of four selective antigens, such as Uracil-DNA glycosylase, were significant higher in sera of colon cancers than in normal sera. These data indicated that the counterpart auto-antibodies may be serological biomarkers of colon malignancy.

关 键 词：结肠癌 肿瘤抗原 自身抗体 CDNA表达文库 血清标志物 

分 类 号：R730.3[医药卫生—肿瘤]