Abstract 550: Evaluation of NQO1 as a potential diagnostic marker for bladder cancer

Abstract

Abstract The present method for detection of bladder cancer involves ultrasonography followed by cystoscopy. This process is time intensive, requires skilled personnel and is unpleasant for the patient as a result of its invasive nature. This results in patient drop-out and patients that have recovered from bladder cancer are lost to follow-up due to the necessity for hospital visits for monitoring. We have used a novel test in order to monitor NAD(P)H quinone oxidoreductase 1 (NQO1) activity in cells recovered from routine urine samples since expression of NQO1 has previously been reported to be increased in several tumour types including transitional cell carcinoma of the bladder. Informed consent and urine samples were obtained from 73 bladder cancer patients and 42 age-matched bladder cancer-negative outpatients at the University Hospital of Wales, Cardiff. Live exfoliated cells were collected from the urine and assessed for their ability to metabolise an NQO1-specific substrate into a highly fluorescent product. Fluorescence intensity was then measured in a simple, inexpensive instrument. Results were checked against clinical correlates, bladder cancer stage, age, medication, and smoking status. Initial tests in cell lines showed excellent correlation with NQO1 levels detected by other methods. We found that in patient samples, while cell numbers in urine and expression of NQO1 per cell were not in themselves significant, NQO1 per ml of urine was highly significantly increased in bladder cancer patients (p = 0.009). Further, NQO1 was higher in patients that had high grade tumours as described in the WHO 2004 guidelines (p = 0.003). The sensitive fluorescence-based method to detect NQO1 activity in exfoliated urothelial cells shows exceptional promise in the development of rapid, non-invasive bladder cancer diagnostics. The method will be used on larger numbers of samples in order to be able to verify these initial findings. Note: This abstract was not presented at the meeting. Citation Format: Simone Cuff, Ruth Lewis, Mohammed Jaffar, Richard Knox, Ian Weeks. Evaluation of NQO1 as a potential diagnostic marker for bladder cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 550. doi:10.1158/1538-7445.AM2015-550