Autoantibodies to annexin XI-A and other autoantigens in the diagnosis of breast cancer
Autoantibodies to annexin XI-A and other autoantigens in the diagnosis of breast cancer
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DOI：
10.1158/0008-5472.can-03-0932
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发表时间：
2004-08-01
期刊：
影响因子：
11.2
通讯作者：
Karvonen, RL
中科院分区：
文献类型：
--
作者：
Fernández-Madrid, F;Tang, NM;Karvonen, RL
我们报告了乳腺癌患者血清中普遍识别的自身抗原的鉴定。我们从10例自身抗体滴度较高的乳腺浸润性导管癌(IDC)患者血清中筛选出T7噬菌体乳腺癌基因展示文库。一种高通量的方法包括组装编码潜在乳腺癌自身抗原的938个T7噬菌体。用90例乳腺癌患者[乳腺导管原位癌(DCIS)15例，乳腺IDC患者75例]、51例非癌对照血清和21例系统性自身免疫病患者血清，对阳性噬菌体芯片进行了检测。一个12噬菌体乳腺癌预测小组是用乳腺癌患者血清识别的噬菌体插入构建的，而不是非癌症或自身免疫对照血清识别的(P<；0.0001)。几种自身抗原，包括Annexin XI-A、Ku抗原的p80亚基、核糖体蛋白S6和其他未知自身抗原，可以显著区分乳腺癌和非癌症对照血清。用三种不同的血清进行生物扫描，克隆了与Annexin XI-A相同的部分cDNA序列。19%的乳腺癌患者血清中有19%的抗体与Annexin XI-A的41-74位氨基酸发生反应，而60%的乳腺DCIS患者血清中存在抗体。此外，与Annexin XI-A相同的部分序列、与PKI-67叉头相关(FHA)结构域相互作用的核仁蛋白、KIAA1671基因产物、核糖体蛋白S6、细胞周期蛋白K、延伸因子-2、Grb2相关蛋白2以及其他未知蛋白可以区分DCIS和IDC，有可能成为乳腺癌诊断的潜在生物标志物。
We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput method involved the assembly of 938 T7 phages encoding potential breast cancer autoantigens. Microarrays of positive phages were probed with sera from 90 patients with breast cancer [15 patients with ductal carcinoma in situ (DCIS) and 75 patients with IDC of the breast], with 51 non-cancer control sera and with sera from 21 patients with systemic autoimmune diseases. A 12-phage breast cancer predictor group was constructed with phage inserts recognized by sera from patients with breast cancer and not by non-cancer or autoimmune control sera (P < 0.0001). Several autoantigens including annexin XI-A, the p80 subunit of the Ku antigen, ribosomal protein S6, and other unknown autoantigens could significantly discriminate between breast cancer and non-cancer control sera. Biopanning with three different sera led to the cloning of partial cDNA sequences identical to annexin XI-A. IgG autoantibodies reacting with the amino acid 41-74 sequence of annexin XI-A were found in 19% of all women with breast cancer but in 60% of sera from women with DCIS of the breast. In addition, partial sequences identical to annexin XI-A, nucleolar protein interacting with the forkhead-associated (FHA) domain of pKi-67, the KIAA1671 gene product, ribosomal protein S6, cyclin K, elongation factor-2, Grb2-associated protein 2, and other unknown proteins could distinguish DCIS from IDC of the breast and appear to be potential biomarkers for the diagnosis of breast cancer.