Qin Jie-Jie, Wang Xiao-Rui, Wang Peng, Ren Peng-Fei, Shi Jian-Xiang, Zhang Hong-Fei, Xia Jun-Fen, Wang Kai-Juan, Song Chun-Hua, Dai Li-Ping, Zhang Jian-Ying
Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China E-mail :
Asian Pac J Cancer Prev. 2014;15(6):2635-40. doi: 10.7314/apjcp.2014.15.6.2635.
Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.
癌症患者的血清中可能含有与一组独特的自体细胞抗原发生反应的抗体,这些抗原被称为肿瘤相关抗原(TAAs)。本研究旨在确定多种TAA的微阵列是否会增强抗体检测能力,以及是否是一种用于食管癌检测和诊断的有效方法。我们的多种TAA微阵列由11种抗原组成,即p53、p16、Impl、细胞周期蛋白B1、C-myc、RalA、p62、生存素、Koc、细胞周期蛋白D1和细胞周期蛋白E全长重组蛋白。采用酶联免疫吸附测定(ELISA)法检测174例食管癌患者血清以及242例正常个体血清中针对11种选定TAA的自身抗体。此外,ELISA的阳性结果通过蛋白质印迹法进行了确认。在一项平行筛选试验中,随着抗原依次添加至最终总共11种TAA,阳性抗体反应呈逐步增加。这11种TAA是最佳的平行组合,诊断食管癌的灵敏度和特异度分别为75.3%和81.0%。阳性预测值和阴性预测值分别为74.0%和82.0%,表明11种TAA的平行检测显著提高了诊断精度。此外,在食管癌的不同阶段,针对7种抗原(包括p53、Impl、C-myc、RalA、p62、生存素和细胞周期蛋白D1)的抗体水平存在显著差异,这表明自身抗体可能参与了食管癌的发病机制和进展过程。总而言之,本研究进一步支持了我们之前的假设,即抗体组合可能对某些类型癌症的诊断具有更高的灵敏度。定制的多种精心挑选的TAA微阵列能够增强食管癌免疫诊断中的自身抗体检测能力,并且针对TAA的自身抗体可能是临床分期的参考指标。