Peptide Mimic Isolated by Autoantibody Reveals Human Arrest Defective 1 Overexpression Is Associated with Poor Prognosis for Colon Cancer Patients

Tumor-associated antigens, which induce the generation of autoantibodies, are useful as cancer biomarkers in early detection and prognostic prediction of cancer. To isolate a novel cancer marker, we used serum antibodies from colon cancer patients to screen a phage display peptide library. A positive peptide 249C (VPLYSNTLRYGF) that could specifically react with serum from colon cancer patients was isolated, and the corresponding antigen-human arrest defective 1 (ARD1A), which shares an identical LYSNTL motif with 249C, was identified. Both immunological assays and three-dimensional structure analysis showed that the LYSNTL region is an epitope of ARD1A. Using ELISA and immunohistochemistry, we found anti-ARD1A antibody levels in serum from patients with colon cancer were significantly higher than those in healthy volunteers (P < 0.001), and ARD1A expression was detected in 84.1% (227/270) of colon cancer tissues compared with 22.7% (55/242) of matched noncancerous tissues (P < 0.001) and 4.8% (2/42) of benign lesions (P < 0.001). Furthermore, multivariate analysis with Cox proportional hazards regression models revealed that ARD1A-positive patients had significantly shortened overall survival (OS) (HR, 1.91, P = 0.039) and borderline significantly shortened disease-free survival (DFS) (HR, 1.70; P = 0.068). Kaplan-Meier survival curves also showed that ARD1A expression was associated significantly with shortened DFS (P = 0.037) and OS (P = 0.019). These results indicate that ARD1A is a novel tumor-associated antigen and a potential prognostic factor for colon cancer.