Abstract
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.
Highlights
Estimated 482,300 new esophageal cancer cases and 406,800 deaths occurred in 2008 worldwide, and the highest rates were found in Southern and Eastern Africa and Eastern Asia (Jemal et al, 2011)
A mini-array of eleven tumor-associated antigens (TAAs) was used as coating antigens in Enzyme-linked immunosorbent assays (ELISA), and sera from 174 patients with esophageal cancer and sera from 242 normal
Mini-Array of Multiple Tumor-associated Antigens (TAAs) in the Immunodiagnosis of Esophageal Cancer individuals were examined for the presence of antibodies to the individual TAA and cumulatively to the entire panel of eleven TAAs
Summary
Estimated 482,300 new esophageal cancer cases and 406,800 deaths occurred in 2008 worldwide, and the highest rates were found in Southern and Eastern Africa and Eastern Asia (Jemal et al, 2011). Esophageal cancer is one of the most common malignancies of the digestive tract and the fourth most frequent causes of cancer deaths in China (He et al, 2011). Esophageal cancer shows a poor prognosis largely due to the lack of early screening strategy and is often presented in an advanced stage at the first time of diagnosis (Shang et al, 2010). Extensive studies have been conducted to identify and validate new biomarkers to increase the sensitivity and specificity of esophageal cancer detection. Despite the high sensitivity of 80%, the diagnostic value of this method for esophageal cancer of human is still in question
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