Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker.

Sunga Choi,Hee Kyoung Joo,Yu Ran Lee,Byeong Hwa Jeon,Jae Sung Lim,Ju Hyun Shin,Seok Jong Chang,Yong Gil Na,Ki Hak Song

doi:10.1155/2016/7276502

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.

Highlights

Bladder cancer (BCa) is the second most common of all genitourinary malignancies in the United States [1] and Korea [2]
receiver operating characteristics (ROC) analysis of control versus BCa groups (Figure 1(b)) yielded an area under the curve (AUC) of 0.83; the ROC curve and corresponding AUC show that urine APE1/Ref1 as a biomarker has the predictive ability to discriminate between patients with BCa and normal subjects
To measure urinary APE1/Ref-1 levels, we modified an APE1/Ref-1 enzyme-linked immunosorbent assay (ELISA) that was initially developed for the detection of serum APE1/Ref-1 [10]

Summary

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 superficial urothelial carcinoma can expect a 5-year survival rate of more than 90% [3]. 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 [5,6,7,8,9]

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Conclusion