title: Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker.
abstract: 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 significantly 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. The 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. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.
authors.affiliation: Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
authors.forename: Sunga
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
authors.forename: Yu Ran
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Joo
authors.affiliation: Department of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.
authors.forename: Ki Hak
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.
authors.forename: Yong Gil
authors.initials: YG
authors.lastname: Na
authors.affiliation: Department of Physiology, College of Medicine, Seonam University, Namwon 55724, Republic of Korea.
authors.forename: Seok Jong
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Department of Urology, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000652:urine*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase