title: Value of urinary topoisomerase-IIA cell-free DNA for diagnosis of bladder cancer.
abstract: OBJECTIVE
  Topoisomerase-II alpha (TopoIIA ), a DNA gyrase isoform that plays an important role in the cell cycle, is present in normal tissues and various human cancers, and can show altered expression in both. The aim of the current study was to examine the value of urinary TopoIIA cell-free DNA as a noninvasive diagnosis of bladder cancer (BC).
  
  
  METHODS
  Two patient cohorts were examined. Cohort 1 (73 BC patients and seven controls) provided bladder tissue samples, whereas cohort 2 (83 BC patients, 54 nonmalignant hematuric patients, and 61 normal controls) provided urine samples. Real-time quantitative polymerase chain reaction was used to measure expression of TopoIIA mRNA in tissues and TopoIIA cell-free DNA in urine samples.
  
  
  RESULTS
  The results showed that expression of TopoIIA mRNA in BC tissues was significantly higher than that in noncancer control tissues (p<0.001). The expression of urinary TopoIIA cell-free DNA in BC patients was also significantly higher than that in noncancer patient controls and hematuria patients (p < 0.001 and p < 0.001, respectively). High expression of urinary TopoIIA cell-free DNA was also detected in muscle invasive bladder cancer (MIBC) when compared with nonmuscle invasive bladder cancer (NMIBC) (p=0.002). Receiver operating characteristics (ROC) curve analysis was performed to examine the sensitivity/specificity of urinary TopoIIA cell-free DNA for diagnosing BC, NMIBC, and MIBC. The areas under the ROC curve for BC, NMIBC, and MIBC were 0.741, 0.701, and 0.838, respectively.
  
  
  CONCLUSIONS
  In summary, the results of this study provide evidence that cell-free TopoIIA DNA may be a potential biomarker for BC.
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Ye-Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Chunri
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Il-Seok
authors.initials: IS
authors.lastname: Lee
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Xuan-Mei
authors.initials: XM
authors.lastname: Piao
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Byun
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Pildu
authors.initials: P
authors.lastname: Jeong
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000652:urine*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D016022:Case-Control Studies; D002474:Cell-Free System; D015331:Cohort Studies; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000652:urine*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000652:urine*; D005260:Female; D015870:Gene Expression; D006417:Hematuria / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D004250:DNA Topoisomerases, Type II
keywords: Biomarkers; DNA topoisomerase II alpha; Hematuria; Urinary bladder neoplasms; Urine