Abstract 4619: Oncoprotein DEK as a tissue and urinary biomarker for bladder cancer

Abstract

Abstract Bladder cancer is a significant healthcare problem in the USA with a high recurrence rate. More than 90% of bladder cancers are transitional cell carcinomas (TCC). About 75% of TCC present as superficial tumors, of which 50-70% of tumors will recur and roughly 10-20% will progress to aggressive invasive disease. Early detection of bladder cancer is essential for removing the tumor with preservation of the bladder, avoiding metastasis and hence improving prognosis and long-term survival. Urine-based detection of bladder cancer biomarkers aim to reduce the use of current invasive procedure; cystoscopy for diagnosis and surveillance of bladder cancer. No single bladder tumor marker has emerged as the generally accepted test of choice when compared to cystoscopy. As a result, there is a growing need to identify new biomarkers to further develop urine-based bladder cancer diagnostic tests. The oncoprotein DEK is one such candidate biomarker for bladder cancer. Human DEK was first characterized as part of a DEK-CAN fusion resulting from chromosomal translocation in a subset of patients with acute myeloid leukemia. Subsequent studies identified DEK as an over expressed gene in several malignancies including bladder cancer. However, there are no reports to show the presence of the DEK protein in urine of bladder cancer patients. To evaluate if DEK is a biomarker for bladder cancer, we analyzed the expression of DEK protein in 26 TCC tumor tissues and adjacent normal tissue by western blot analysis using a monoclonal DEK antibody. Our results indicate that DEK is expressed in 85% of analyzed tumors but not in normal tissues. As urine contains both cells exfoliated from normal and cancerous urothelium as well as proteins from either secretion or cell lysis, we determined if the DEK protein is present in urine of bladder cancer patients. We analyzed approximately 30 urine samples from patients with active bladder cancer, other malignant urogenital disease and healthy individuals. Urine samples were precipitated with acetone and re-suspended precipitates were analyzed for DEK expression by western blot analysis using polyclonal DEK antibody. We are the first to show that DEK is present in the urine of bladder cancer patients with assay specificity of 86% and sensitivity of 84%. Overall, our data suggest that DEK protein is a biomarker for bladder cancer and the presence of DEK protein in urine of bladder cancer patient can be explored as a diagnostic test for bladder cancer. Successful development of a sensitive test that detects DEK protein in urine samples will allow clinicians to monitor patients with history of bladder cancer and for screening of high-risk populations, such as smokers or workers exposed to industrial bladder carcinogens and reduce the use of invasive cystoscopy, increase patient compliance and survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4619.