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

Richard Bryan, Wenbin Wei, Neil Shimwell, Stuart Collins, Syed Hussain, Lucinda Billingham, Paul Murray, N Deshmukh, Nicholas James, DM Wallace, Philip Johnson, Maurice Zeegers, Kar Cheng, Ashley Martin, Douglas Ward

Research output: Contribution to journalArticle

26 Citations (Scopus)


Purpose: 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. Experimental design: 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 and clinical relevance: 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.
Original languageEnglish
Pages (from-to)493-503
Number of pages11
JournalProteomics. Clinical applications
Issue number9-10
Publication statusPublished - 1 Oct 2011


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  • Bladder cancer prognosis

    Bryan, R. & Ward, D., 2 Jun 2016, IPC No. G01N 33/574 (2006.01), G01N 33/68 (2006.01), Patent No. WO/2016/083832, Priority date 28 Nov 2014, Priority No. US 62/085,433

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