title: Tumour expression of bladder cancer-associated urinary proteins.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The current basis for diagnosis and prognosis in urinary bladder cancer is based on the pathologists' assessment of a biopsy of the tumour. Urinary biomarkers are preferable as they can be non-invasively sampled. Urinary cytology is the only test with widespread use but is hampered by poor reproducibility and low sensitivity. By studying the protein expression in bladder tumour tissue samples of proteins previously found in elevated levels in the urine of patients with bladder cancer, we have been able to show that these proteins originate from the tumour. The immunoreactivity of three of the investigated proteins increased with higher stage. Also a serine peptidase inhibitor was found to be predictive of progression from non-muscle-invasive to muscle-invasive tumours.
  
  
  OBJECTIVE
  To analyse the expression of five bladder cancer-associated urinary proteins and investigate if expression is related to the malignant phenotype of the tumour. To explore the possible prognostic value of these proteins.
  
  
  METHODS
  Urine samples, 16 from patients with bladder cancer and 26 from controls, were used in Western Blotting experiments. Tissue microarrays with bladder tissue from 344 patients diagnosed with bladder cancer between 1984 and 2005 was used in immunohistochemistry experiments. The proteins apolipoprotein E (APOE), fibrinogen β chain precursor (FGB), leucine-rich α2-glycoprotein (LRG1), polymerase (RNA) I polypeptide E (POLR1E), α1-antitrypsin (SERPINA1) and topoisomerase 2A (TOP2A) were probed with antibodies validated by the Human Protein Atlas.
  
  
  RESULTS
  Increased expressions of APOE, FGB and POLR1E were correlated with increased tumour stage (P < 0.001). Expression of SERPINA1 in Ta and T1 tumours was found to increase the risk of tumour progression (hazard ratio 2.57, 95% confidence interval 1.13-5.87; P = 0.025) CONCLUSIONS: All proteins previously detected in urine from patients with bladder cancer were also expressed in bladder cancer tissue. The expression of APOE, FGB and POLR1E increased with stage and they are potential diagnostic markers. SERPINA1 was identified as a prognostic marker candidate.
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. marten.linden@surgsci.uu.se
authors.forename: Mårten
authors.initials: M
authors.lastname: Lindén
authors.forename: Ulrika
authors.initials: U
authors.lastname: Segersten
authors.forename: Marcus
authors.initials: M
authors.lastname: Runeson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wester
authors.forename: Christer
authors.initials: C
authors.lastname: Busch
authors.forename: Ulf
authors.initials: U
authors.lastname: Pettersson
authors.forename: Sara Bergström
authors.initials: SB
authors.lastname: Lind
authors.forename: Per-Uno
authors.initials: PU
authors.lastname: Malmström
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000652:urine*
chemical_list: D009363:Neoplasm Proteins
keywords: bladder cancer; immunohistochemistry; tissue microarray; urinary protein markers