Serum antibodies specific for tumor antigens in colorectal cancer may be useful diagnostic biomarkers

Abstract

10041 Background: Colorectal cancer is immunogenic as evidenced by the presence of antibodies specific to tumor antigens in patient serum and T cell infiltration at the tumor site predicting favorable disease outcome. We questioned whether antibody immunity to tumor associated antigens (TAA) in patients with colorectal cancer could be used as a biomarker to predict disease. Methods: We evaluated serum samples for the presence of antibody immunity to six tumor antigens, cyclin D1, HER-2/neu, insulin-like growth factor binding protein 2 (IGFBP2), NY-ESO-1, p53, and topoisomerase-IIα (TOPO2α), in colorectal cancer patients (n=40) and normal donors (n=200) using ELISA. We then evaluated the diagnostic value of these potential biomarkers by measuring antibody levels to these TAA in an independent sample set which included 30 colorectal cancer patients and 135 normal donors. The samples were judged as positive or negative for colorectal cancer using measurements derived either from a single marker or a combination of the markers. Receiver operating characteristic (ROC) plots were generated to determine the diagnostic accuracy of each test. Results: Colorectal cancer patients had increased levels of antibodies to p53 (p=0.002), TOPO2α (p<0.001), and IGFBP2 (p<0.001) compared to controls. By using a combination of just two antibody measurements, TOPO2α and IGFBP2, we could discriminate colorectal cancer patients from controls with a diagnostic power of 0.775 as estimated by the area under ROC curve. At a cutoff point of 0.03 mcg/ml TAA specific IgG, the sensitivity was 100% and the specificity was 58%. Conclusions: Serum antibodies to colorectal cancer related antigens may serve as useful biomarkers for colorectal cancer diagnosis. No significant financial relationships to disclose.