title: Hedgehog pathway activation in human transitional cell carcinoma of the bladder.
abstract: BACKGROUND
  The Hedgehog (Hh) signalling pathway functions as an organiser in embryonic development. Recent studies have shown constitutive activation of this pathway in various malignancies, but its role in bladder cancer remains poorly studied.
  
  
  METHODS
  Expression levels of 31 genes and 9 microRNAs (miRNAs) involved in the Hh pathway were determined by quantitative real-time RT-PCR in 71 bladder tumour samples (21 muscle-invasive (MIBC) and 50 non-muscle-invasive (NMIBC) bladder cancers), as well as in 6 bladder cancer cell lines.
  
  
  RESULTS
  The SHH ligand gene and Gli-inducible target genes (FOXM1, IGF2, OSF2, H19, and SPP1) were overexpressed in tumour samples as compared with normal bladder tissue. SHH overexpression was found in 96% of NMIBC and 52% of MIBC samples, as well as in two bladder cancer cell lines. Altered expression of miRNAs supported their oncogene or tumour-suppressor gene status. In univariate analysis, high expression levels of PTCH2, miRNA-92A, miRNA-19A, and miRNA-20A were associated with poorer overall survival in MIBC (P=0.02, P=0.012, P=0.047, and P=0.036, respectively).
  
  
  CONCLUSIONS
  We observed constitutive activation of the Hh pathway in most NMIBC and about 50% of MIBC. We also found that some protein-coding genes and miRNAs involved in the Hh pathway may have prognostic value at the individual level.
authors.affiliation: Department of Urology, Service d'Urologie, Université Paris Descartes, Sorbonne Paris Cité, 27 rue du Faubourg Saint Jaques, Paris F-75014, France. gg_pignot@yahoo.fr
authors.forename: G
authors.initials: G
authors.lastname: Pignot
authors.forename: A
authors.initials: A
authors.lastname: Vieillefond
authors.forename: S
authors.initials: S
authors.lastname: Vacher
authors.forename: M
authors.initials: M
authors.lastname: Zerbib
authors.forename: B
authors.initials: B
authors.lastname: Debre
authors.forename: R
authors.initials: R
authors.lastname: Lidereau
authors.forename: D
authors.initials: D
authors.lastname: Amsellem-Ouazana
authors.forename: I
authors.initials: I
authors.lastname: Bieche
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D000072079:Patched Receptors; D000072082:Patched-2 Receptor; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D035683:MicroRNAs; C000606238:PTCH2 protein, human; D000072079:Patched Receptors; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface