title: Stage, grade and behavior of bladder urothelial carcinoma defined by the microRNA expression profile.
abstract: OBJECTIVE
  We identified miRNA expression profiles in urothelial carcinoma that are associated with grade, stage, and recurrence-free and disease specific survival.
  
  
  METHODS
  The expression of 14 miRNAs was evaluated by quantitative reverse transcriptase-polymerase chain reaction in surgical specimens from 30 patients with low grade, noninvasive (pTa) and 30 with high grade, invasive (pT2-3) urothelial carcinoma. Controls were normal bladder tissue from 5 patients who underwent surgical treatment for benign prostatic hyperplasia. Endogenous controls were RNU-43 and RNU-48. miRNA profiles were compared and Kaplan-Meier curves were constructed to analyze disease-free and disease specific survival.
  
  
  RESULTS
  miR-100 was under expressed in 100% of low grade pTa specimens (p <0.001) and miR-10a was over expressed in 73.3% (p <0.001). miR-21 and miR-205 were over expressed in high grade pT2-3 disease (p = 0.02 and <0.001, respectively). The other miRNAs were present at levels similar to those of normal bladder tissue or under expressed in each tumor group. miR-21 over expression (greater than 1.08) was related to shorter disease-free survival in patients with low grade pTa urothelial carcinoma. Higher miR-10a levels (greater than 2.30) were associated with shorter disease-free and disease specific survival in patients with high grade pT2-3 urothelial carcinoma.
  
  
  CONCLUSIONS
  Four miRNAs were differentially expressed in the 2 urothelial carcinoma groups. miR-100 and miR-10a showed under expression and over expression, respectively, in low grade pTa tumors. miR-21 and miR-205 were over expressed in pT2-3 disease. In addition, miR-10a and miR-21 over expression was associated with shorter disease-free and disease specific survival. miRNAs could be incorporated into the urothelial carcinoma molecular pathway. These miRNAs could also serve as new diagnostic or prognostic markers and new target drugs.
authors.affiliation: Laboratory of Medical Investigation, Urology Department, University of São Paulo Medical School, São Paulo, Brazil. nelson.dip@hotmail.com
authors.forename: Nelson
authors.initials: N
authors.lastname: Dip
authors.forename: Sabrina T
authors.initials: ST
authors.lastname: Reis
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Timoszczuk
authors.forename: Nayara I
authors.initials: NI
authors.lastname: Viana
authors.forename: Camila B
authors.initials: CB
authors.lastname: Piantino
authors.forename: Denis R
authors.initials: DR
authors.lastname: Morais
authors.forename: Caio M
authors.initials: CM
authors.lastname: Moura
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Abe
authors.forename: Iran A
authors.initials: IA
authors.lastname: Silva
authors.forename: Miguel
authors.initials: M
authors.lastname: Srougi
authors.forename: Marcos F
authors.initials: MF
authors.lastname: Dall'Oglio
authors.forename: Katia R M
authors.initials: KR
authors.lastname: Leite
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D035683:MicroRNAs