title: High insulin-like growth factor mRNA-binding protein 3 (IMP3) protein expression is associated with poor survival in muscle-invasive bladder cancer.
abstract: What's known on the subject? and What does the study add? Insulin-like growth factor mRNA-binding protein 3 (IMP3) is an oncofetal protein found to be re-expressed in a series of human cancers including bladder cancer. In vitro analyses showed an invasion and proliferation promoting effect for IMP3. Further in vitro studies suggested that IMP3 is able to bind to the mRNAs of CD44 and insulin-like growth factor 2 (IGF2), enhancing their stability and expression. However, this molecular interaction has not yet been analysed in tumour samples. In the present study, we identified for the first time high IMP3 tissue protein expression as an independent predictor of poor patients' survival in muscle-invasive bladder cancer. Furthermore, there was no correlation between IMP3 and its molecular targets in bladder carcinoma specimens and concluded that the tumour-promoting effect of IMP3 is not related to its regulatory action on IGF2 and CD44.
  
  
  OBJECTIVE
  To assess the prognostic value and molecular actions of the oncofetal protein insulin-like growth factor mRNA-binding protein 3 (IMP3) in muscle-invasive bladder cancer (BC).
  
  
  METHODS
  IMP3 expression was analysed by immunohistochemistry, real-time polymerase chain reaction and Western blot analysis in 224 patients with BC. The molecular targets of IMP3; CD44, insulin-like growth factor 2 (IGF2) and its receptor the IGF1 receptor (IGF1-R) were also investigated. Expression levels were correlated with clinical follow-up data by using both univariate and multivariate Cox regression analyses.
  
  
  RESULTS
  IMP3 mRNA and protein levels were significantly elevated in high-stage and high-grade muscle-invasive BC. In muscle-invasive BC IMP3 protein but not gene expression proved to be an independent predictor of disease-specific (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.28-4.56, P = 0.004) and overall survival (HR 2.07, 95% CI 1.12-3.82, P = 0.020). The expression levels of IGF2 and CD44 showed no correlation with that of IMP3.
  
  
  CONCLUSIONS
  High IMP3 protein levels may identify patients with BC at high risk of disease progression and may therefore select patients for a more intensive therapy or for a strict follow-up. Its high expression in high-grade bladder carcinoma cells makes IMP3 for an attractive target for therapy. The tumour promoting effect of IMP3 is independent from its regulatory action on IGF2 and CD44 expression.
authors.affiliation: Department of Urology, University of Duisburg-Essen, Duisburg, Germany. sztibusz@gmail.com
authors.forename: Tibor
authors.initials: T
authors.lastname: Szarvas
authors.forename: Frank
authors.initials: F
authors.lastname: vom Dorp
authors.forename: Christian
authors.initials: C
authors.lastname: Niedworok
authors.forename: Ariane
authors.initials: A
authors.lastname: Melchior-Becker
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.forename: Bernhard B
authors.initials: BB
authors.lastname: Singer
authors.forename: Henning
authors.initials: H
authors.lastname: Reis
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Bánkfalvi
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
authors.forename: Imre
authors.initials: I
authors.lastname: Romics
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
authors.forename: Herbert
authors.initials: H
authors.lastname: Rübben
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis*; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger