Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q
Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q
复制标题
DOI：
10.1002/ijc.10900
复制
发表时间：
2003-03-10
影响因子：
6.4
通讯作者：
Nelson, BH
中科院分区：
文献类型：
--
作者：
Stone, B;Schummer, M;Nelson, BH
我们利用SEREX免疫筛选来鉴定一组与人浆液性卵巢癌相关的新型肿瘤抗原，这些抗原可能被证明对这种疾病的早期检测和治疗有用。用来自25名晚期卵巢癌患者的血清组对3个独立cDNA文库进行广泛筛选，鉴定出一组9种抗原，其在超过1名患者中具有免疫原性，而在20-45名正常女性血清供体组中没有。这些抗原包括p53、NY-ESO-1、UBQLN 1、HOXB 6、TOP 2A、推定解旋酶-RUVBL（RUVBL）、HMBA诱导型（HEXIM 1）、DDX 5和HDCMA。25例卵巢癌患者中有10例（40%）表达至少1种这些抗原的血清IgG，而14%（4/25）有2种或2种以上抗原的抗体。出乎意料的是，在该筛选中鉴定的4种抗原DDX 5、HEXIM 1、TOP 2A和HOXB 6在17 q区域内编码，该区域还包括HER 2/neu、同源框-137和BRCA 1的基因。实时RT-PCR分析显示，HER 2/neu和3种SEREX定义的抗原，TOP 2A，HOXB 6和DDX 5的mRNA在卵巢肿瘤中比大多数正常组织（包括正常和良性卵巢组织）更丰富，表明17号染色体该区域内编码的基因表达升高是卵巢肿瘤中的常见事件。因此，这些异常表达模式与内源性免疫应答相结合表明这些抗原代表了免疫治疗的潜在靶点。(C)2002 Wiley-Liss，Inc.
We utilized SEREX immunoscreening to identify a set of novel tumor antigens that are associated with human serous ovarian cancer and may prove useful for the early detection and treatment of this disease. Extensive screening with a panel of sera from 25 late-stage ovarian cancer patients against 3 independent cDNA libraries identified a set of 9 antigens that were immunogenic in more than 1 patient and not in a panel of 20-45 normal female serum donors. These antigens include p53, NY-ESO-1, UBQLN1, HOXB6, TOP2A, putative helicase-RUVBL (RUVBL), HMBA-inducible (HEXIM1), DDX5 and HDCMA. Ten of 25 ovarian cancer patients (40%) expressed serum IgG to at least 1 of these antigens, while 14% (4/25) had antibodies to 2 or more antigens. Unexpectedly, 4 antigens identified in this screen, DDX5, HEXIM1, TOP2A and HOXB6, are encoded within a region of 17q that also includes the genes for HER2/neu, Homeobox-137 and BRCA1. Real-time RT-PCR analysis showed that mRNA for HER2/neu and 3 SEREX-defined antigens, TOP2A, HOXB6 and DDX5, was more abundant in ovarian tumors than most normal tissues, including normal and benign ovarian tissues, suggesting that elevated expression of genes encoded within this region of chromosome 17 is a common event in ovarian tumors. Thus, these abnormal expression patterns combined with the endogenous immune response suggests that these antigens represent potential targets for immunotherapy. (C) 2002 Wiley-Liss, Inc.