Research Article Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker Sunga Choi, 1 Ju Hyun Shin, 2 Yu Ran Lee, 1 Hee Kyoung Joo, 1 Ki Hak Song, 2 Yong Gil Na, 2 Seok Jong Chang, 3 Jae Sung Lim, 2 and Byeong Hwa Jeon 1 1 Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea 2 Department of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea 3 Department of Physiology, College of Medicine, Seonam University, Namwon 55724, Republic of Korea Correspondence should be addressed to Jae Sung Lim; uro17@cnuh.co.kr and Byeong Hwa Jeon; bhjeon@cnu.ac.kr Received 15 September 2015; Accepted 4 January 2016 Academic Editor: Felix Chun Copyright © 2016 Sunga Choi et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were signifcantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. Te receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. Te optimal combination of sensitivity and specifcity was determined to be 82% and 80% at a cut-of value of 0.376 ng/100 L for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fuids would be clinically applicable for diagnosis of BCa. 1. Introduction Bladder cancer (BCa) is the second most common of all genitourinary malignancies in the United States [1] and Korea [2]. Most individuals with BCa who are diagnosed early, show no muscle invasion, and have superfcial urothelial carcinoma can expect a 5-year survival rate of more than 90% [3]. If the BCa is invasive, however, with tumor cells spreading beyond the bladder to the surrounding tissue or to nearby lymph nodes, or organs, signs of late stage BCa, the 5-year survival rate drops sharply. Terefore, early intervention can dramatically increase the probability of a BCa patient’s survival. Patients with noninvasive BCa frequently show a high rate of recurrence and progression of the disease within 2 years of transurethral resection [4], and continuous follow-up testing is required. Several studies have focused on the development of tools for the diagnosis and prognosis of BCa using urinary biomarkers [5–9]. In our previous report, we proposed a new BCa diagnostic protein, apurinic/apyrimidinic endonuclease 1/redox factor- 1 (APE1/Ref-1) in serum [10]. APE1/Ref-1 protein was origi- nally identifed as a multifunctional protein involved in DNA repair and redox signaling. APE1/Ref-1 levels were found to be elevated with dysregulated cellular proliferation, as is typ- ically seen in cancers [10–12]. APE1/Ref-1 is mainly localized in the nucleus and shows dynamic shuttling between the nucleus and cytoplasm in response to various stress stimuli. Furthermore, extracellular secretion of APE1/Ref-1 into the circulation suggests this protein could be used as a serologic biomarker [13, 14]. APE1/Ref-1 secretion from cells is also supported by the presence of autoantibody against APE1/Ref- 1 in the blood of patients with lung cancer [15] and systemic lupus erythematosus [16]. Te clinical need for specifc and sensitive urothelial tumor diagnostics remains as urgent issue. Te ideal diag- nostics would measure the level of a BCa protein biomarker Hindawi Publishing Corporation Disease Markers Volume 2016, Article ID 7276502, 8 pages http://dx.doi.org/10.1155/2016/7276502