Latvian Biomedical Research and Study Centre, Riga, Latvia.
Int J Cancer. 2013 Jan 1;132(1):137-47. doi: 10.1002/ijc.27667. Epub 2012 Jul 3.
Autoantibodies against tumor-associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display-based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage-antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero-positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150-feature microarray was tested with sera from 100 patients with GC and 100 cancer-free controls, and then the top-ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45-autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.
自身抗体针对肿瘤相关抗原是非常有吸引力的生物标志物，用于开发非侵入性血清学检测，以早期发现癌症，因为它们在血清中的特异性和稳定性。在我们的研究中，我们应用 T7 噬菌体展示基于重组 cDNA 表达文库技术的血清学分析，以鉴定一组在胃癌（GC）患者中引起体液反应的代表性抗原，制作噬菌体-抗原微阵列，并利用它们调查 GC 患者和炎症性疾病患者的自身抗体库。我们开发了数据归一化和截止值确定程序，以定义血清阳性信号，并根据信号强度和反应频率对其进行排序。为了鉴定具有最高诊断价值的自身抗体，我们用 100 例 GC 患者和 100 例无癌症对照者的血清测试了 1150 个特征的微阵列，然后用排名最高的 86 个抗原制作了聚焦阵列，用包含 235 例 GC 患者、154 例消化性溃疡和胃炎患者和 213 例健康对照者血清样本的独立验证集进行测试。受试者工作特征曲线分析表明，45 种自身抗体特征可以区分 GC 和健康对照者，曲线下面积（AUC）为 0.79（59%的敏感性和 90%的特异性），GC 和消化性溃疡的 AUC 为 0.76，GC 和胃炎的 AUC 为 0.64。此外，它可以与晚期 GC 一样敏感地检测早期 GC。有趣的是，自身抗体的产生与组织学类型、H. pylori 状态、分级、肿瘤的定位和大小无关，而似乎与转移疾病有关。
