卵巢癌自身抗体谱研究及应用  

Screening and application of human ovary carcinoma auto-antibody profile

作　　者：冉宇靓[1] 胡海[1] 杨光[1] 遇珑[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生物学及分子生物学室,北京100021

出　　处：《免疫学杂志》2007年第3期243-247,共5页Immunological Journal

基　　金：国家科技攻关计划资助项目(2004BA703B05)

摘　　要：目的肿瘤自身抗原可以诱导机体免疫反应,产生与肿瘤相关的自身抗体。因此,在肿瘤患者血清中存在肿瘤自身抗体谱。本研究拟寻找鉴定卵巢癌自身抗体谱,研究这些自身抗体作为卵巢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,为卵巢癌的免疫治疗提供候选靶抗原。方法用卵巢癌组织建立了库容量达1.82×106pfu的cDNA表达文库,用卵巢癌患者血清进行了文库血清学分析(SEREX),筛选获了阳性抗原克隆,进一步分析了其中5个克隆与48例卵巢癌48例正常人血清的反应情况。结果获得的67个阳性克隆中,5个克隆与已知EST序列明显无同源性,另外49个克隆与已知基因高度同源。BHLHB2等5个抗原克隆与卵巢癌患者和正常人血清反应阳性率分别为41.6%(14.6%)、29.2%(6.25%)、29.2%(12.5%)、31%(18.7%)、31%(6.2%)。联合5个克隆诊断卵巢癌的敏感性为81%,特异性75%。结论本研究发现的45个卵巢癌抗原可能作为卵巢癌诊断新的候选血清学标志物和免疫治疗潜在分子靶点。BHLHB2等5个克隆与卵巢癌患者血清的反应阳性率明显高于正常人的血清,5个克隆联合诊断卵巢癌有较好的敏感性和特异性,其相关自身抗体可作为卵巢癌诊断的血清标志物。Objective To screen the auto-antibody profile of ovary cancer for benefiting the identification of serolngical biomarkers of ovary malignancy, and to identify the auto-antibody-related antigens for finding target antigens of the immunotherapy of ovary cancer. Methods Expressionlibrary of ovary carcinoma was constructed. The established primary library consisting of 1.82×10^6 clones was screened by autologeus serum. The nucleotide of positive clones were sequenced and analyzed by BLAST software on EMBL and GenBank. Further more, serological immunoreactions of 5 positive clones with 48 ovary cancer sera and 48 normal control sere were evaluated. Results Among 67 positive clones, 5 clones were new antigens without homology to any known genes. The other clones were fragments of known genes and some of them were for the first time defined as antigens of ovary cancer. The serological immunoreacfion rates of five selected antigens were 41.6%, 29.2%, 29.2%, 31%, and 31% respectively in ovary cancer sere. While the counterpart rates of these antigens in normal sere were 14.6%, 6.25%, 12.5%, 18.7%, and 6.2% respectively. Conclusion Antigens of the positive clones may be candidate antigens for immunothempy of ovary cancer. Their counterpart auto-antibodies may be candidate serum biomarkers for ovary cancer. The serolngical reaction rates of five selective antigens, such as BHLHB2, are significant higher in sere of ovary cancers than in normal sere. These data indicate that their counterpart auto-antibodies are serological biomarkers of ovary malignancy.

关 键 词：卵巢癌 肿瘤抗原 自身抗体 CDNA表达文库 血清标志物 

分 类 号：R737.31[医药卫生—肿瘤]