title: Assessment of high-throughput high-resolution MALDI-TOF-MS of urinary peptides for the detection of muscle-invasive bladder cancer.
abstract: OBJECTIVE
  There is a need for better biomarkers to both detect bladder cancer and distinguish muscle-invasive (stage T2+) from non-invasive (stage Ta/T1) disease. We assess whether MALDI-TOF-MS of the urine peptidome can achieve this.
  
  
  METHODS
  We analysed urine from 751 patients with bladder cancer and 127 patients without bladder cancer. Endogenous peptide profiling was performed using a Bruker Ultraflextreme MALDI-TOF-MS.
  
  
  RESULTS
  Significant differences were seen between the spectra of urine from patients with and without T2+ disease. Albumin, total protein and haematuria were also elevated in T2+ patients. Haematuria was detected in 39% of patients with Ta/T1 disease and in 77% of patients with T2+ disease. Class prediction models based on MALDI data produced areas under receiver-operator characteristic curves of up to 0.76 but did not significantly outperform a model based on total protein alone. Many peptides significantly associated with invasive disease are fragments of abundant blood proteins and are also associated with haematuria.
  
  
  CONCLUSIONS
  Microscopic haematuria is strongly associated with invasive disease; even traces of blood/plasma strongly influence the urinary peptidome. This needs to be taken into consideration when using 'omic' methods to search for urinary biomarkers as blood proteins may give false-positive results.
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Bryan
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wei
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Shimwell
authors.forename: Stuart I
authors.initials: SI
authors.lastname: Collins
authors.forename: Syed A
authors.initials: SA
authors.lastname: Hussain
authors.forename: Lucinda J
authors.initials: LJ
authors.lastname: Billingham
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
authors.forename: Nayneeta
authors.initials: N
authors.lastname: Deshmukh
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: James
authors.forename: D Michael A
authors.initials: DM
authors.lastname: Wallace
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Johnson
authors.forename: Maurice P
authors.initials: MP
authors.lastname: Zeegers
authors.forename: K K
authors.initials: KK
authors.lastname: Cheng
authors.forename: Ashley
authors.initials: A
authors.lastname: Martin
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Ward
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine; D005260:Female; D006417:Hematuria / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010455:Peptides / Q000652:urine*; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D010455:Peptides