Assessment of high-throughput high-resolution MALDI-TOF-MS of urinary peptides for the detection of muscle-invasive bladder cancer - Abstract

School of Cancer Sciences, University of Birmingham, Birmingham, B15 2TT, UK.


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.

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.

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 ROC 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.

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.

Written by:
Bryan RT, Wei W, Shimwell NJ, Collins SI, Hussain SA, Billingham LJ, Murray PG, Deshmukh N, James ND, Wallace DM, Johnson PJ, Zeegers MP, Cheng K, Martin A, Ward DG.   Are you the author?

Reference: Proteomics Clin Appl. 2011 Aug 1. Epub ahead of print.
doi: 10.1002/prca.201100011

PubMed Abstract
PMID: 21805675 Bladder Cancer Section