Bladder cancer biomarker discovery using global metabolomic profiling of urine

Bryan M. Wittmann, Steven M. Stirdivant, Matthew W. Mitchell, Jacob E. Wulff, Jonathan E. McDunn, Zhen Li, Aphrihl Dennis-Barrie, Bruce P. Neri, Michael V. Milburn, Yair Lotan, Robert L. Wolfert

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Bladder cancer (BCa) is a common malignancy worldwide and has a high probability of recurrence after initial diagnosis and treatment. As a result, recurrent surveillance, primarily involving repeated cystoscopies, is a critical component of post diagnosis patient management. Since cystoscopy is invasive, expensive and a possible deterrent to patient compliance with regular follow-up screening, new non-invasive technologies to aid in the detection of recurrent and/or primary bladder cancer are strongly needed. In this study, mass spectrometry based metabolomics was employed to identify biochemical signatures in human urine that differentiate bladder cancer from non-cancer controls. Over 1000 distinct compounds were measured including 587 named compounds of known chemical identity. Initial biomarker identification was conducted using a 332 subject sample set of retrospective urine samples (cohort 1), which included 66 BCa positive samples. A set of 25 candidate biomarkers was selected based on statistical significance, fold difference and metabolic pathway coverage. The 25 candidate biomarkers were tested against an independent urine sample set (cohort 2) using random forest analysis, with palmitoyl sphingomyelin, lactate, adenosine and succinate providing the strongest predictive power for differentiating cohort 2 cancer from non-cancer urines. Cohort 2 metabolite profiling revealed additional metabolites, including arachidonate, that were higher in cohort 2 cancer vs. non-cancer controls, but were below quantitation limits in the cohort 1 profiling. Metabolites related to lipid metabolism may be especially interesting biomarkers. The results suggest that urine metabolites may provide a much needed non-invasive adjunct diagnostic to cystoscopy for detection of bladder cancer and recurrent disease management.

Original languageEnglish (US)
Article numbere115870
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 26 2014

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Metabolomics
metabolomics
Biomarkers
Tumor Biomarkers
Metabolites
Urinary Bladder Neoplasms
cystoscopy
biomarkers
urine
Cystoscopy
Urine
metabolites
patient compliance
Sphingomyelins
Succinic Acid
sampling
Neoplasms
application coverage
sphingomyelins
neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wittmann, B. M., Stirdivant, S. M., Mitchell, M. W., Wulff, J. E., McDunn, J. E., Li, Z., ... Wolfert, R. L. (2014). Bladder cancer biomarker discovery using global metabolomic profiling of urine. PLoS One, 9(12), [e115870]. https://doi.org/10.1371/journal.pone.0115870

Bladder cancer biomarker discovery using global metabolomic profiling of urine. / Wittmann, Bryan M.; Stirdivant, Steven M.; Mitchell, Matthew W.; Wulff, Jacob E.; McDunn, Jonathan E.; Li, Zhen; Dennis-Barrie, Aphrihl; Neri, Bruce P.; Milburn, Michael V.; Lotan, Yair; Wolfert, Robert L.

In: PLoS One, Vol. 9, No. 12, e115870, 26.12.2014.

Research output: Contribution to journalArticle

Wittmann, BM, Stirdivant, SM, Mitchell, MW, Wulff, JE, McDunn, JE, Li, Z, Dennis-Barrie, A, Neri, BP, Milburn, MV, Lotan, Y & Wolfert, RL 2014, 'Bladder cancer biomarker discovery using global metabolomic profiling of urine', PLoS One, vol. 9, no. 12, e115870. https://doi.org/10.1371/journal.pone.0115870
Wittmann BM, Stirdivant SM, Mitchell MW, Wulff JE, McDunn JE, Li Z et al. Bladder cancer biomarker discovery using global metabolomic profiling of urine. PLoS One. 2014 Dec 26;9(12). e115870. https://doi.org/10.1371/journal.pone.0115870
Wittmann, Bryan M. ; Stirdivant, Steven M. ; Mitchell, Matthew W. ; Wulff, Jacob E. ; McDunn, Jonathan E. ; Li, Zhen ; Dennis-Barrie, Aphrihl ; Neri, Bruce P. ; Milburn, Michael V. ; Lotan, Yair ; Wolfert, Robert L. / Bladder cancer biomarker discovery using global metabolomic profiling of urine. In: PLoS One. 2014 ; Vol. 9, No. 12.
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