title: Global histone H4K20 trimethylation predicts cancer-specific survival in patients with muscle-invasive bladder cancer.
abstract: OBJECTIVE
  •To determine the role of global histone methylation as a prognostic parameter in patients with bladder cancer.
  
  
  METHODS
  •We used a tissue microarray with samples from patients with non-muscle-invasive bladder cancer (NMIBC; n= 161), muscle-invasive bladder cancer (MIBC, n= 127), normal urothelium (NU; n= 31) and bladder cancer metastases (METS; n= 31) to determine global histone methylation (me) levels at histone H3 lysine 4 (H3K4) and H4K20.
  
  
  RESULTS
  •Global histone modification levels (H3K4me1, H3K4me3, H4K20me1, H4K20me2, and H4K20me3) were lower in bladder cancer samples than in NU tissue •Global levels of H3K4me1, H4K20me1, H4K20me2 and H4K20me3 were decreasing from NU over NMIBC and MIBC to METS. •H4K20me1 levels were increased in patients with NMIBC with advanced pTstage and less differentiated bladder cancer. •In patients with MIBC, pTstage was negatively correlated with H3K4me1, H4K20me1 and H4K20me2 levels. •H4K20me3 levels were significantly correlated in a univariate and multivariate model with bladder cancer-specific mortality after radical cystectomy in patients with MIBC.
  
  
  CONCLUSIONS
  •Global histone methylation levels may help to identify patients with bladder cancer with poor prognosis after radical cystectomy.
authors.affiliation: Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Schneider
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rogenhofer
authors.forename: Guido
authors.initials: G
authors.lastname: Fechner
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Alexander
authors.initials: A
authors.lastname: von Ruecker
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology
chemical_list: D006657:Histones