title: Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder.
abstract: OBJECTIVE
  New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on mRNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage > or =T1 disease.
  
  
  METHODS
  RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases.
  
  
  RESULTS
  A combination of the RNAs CDC2, MDK, IGFBP5, and HOXA13 detected 48%, 90%, and 100% of stage Ta, T1, and >T1 TCCs, respectively, at a specificity of 85%. Detection of Ta tumors increased to 60% for primary (non-recurrent) Ta tumors and 76% for Ta tumors > or =1 cm in diameter. Test specificity was 80% for the 20 control patients with urinary tract infections. The combination of CDC2 and HOXA13 distinguished between grade 1 to 2 TCCs and grade 3 or stage > or =T1 TCCs with approximately 80% specificity and sensitivity.
  
  
  CONCLUSIONS
  Simple gene expression signatures can be used as urine markers for the accurate detection and characterization of bladder cancer.
authors.affiliation: Pacific Edge Biotechnology Ltd., Centre for Innovation, University of Otago, Dunedin, New Zealand.
authors.forename: Andrew
authors.initials: A
authors.lastname: Holyoake
authors.forename: Paul
authors.initials: P
authors.lastname: O'Sullivan
authors.forename: Rob
authors.initials: R
authors.lastname: Pollock
authors.forename: Terry
authors.initials: T
authors.lastname: Best
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kajita
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsui
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.forename: Natalie
authors.initials: N
authors.lastname: Kerr
authors.forename: Fernanda
authors.initials: F
authors.lastname: da Silva Tatley
authors.forename: Lisa
authors.initials: L
authors.lastname: Cambridge
authors.forename: Tumi
authors.initials: T
authors.lastname: Toro
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.forename: Parry
authors.initials: P
authors.lastname: Guilford
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000652:urine*; D012334:RNA, Neoplasm / Q000235:genetics / Q000652:urine*; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm