Metabolomic signatures of aggressive prostate cancer

Jonathan E. McDunn, Zhen Li, Klaus Peter Adam, Bruce P. Neri, Robert L. Wolfert, Michael V. Milburn, Yair Lotan, Thomas M. Wheeler

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

BACKGROUND Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. METHODS A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. RESULTS Prostate tumors had significantly altered metabolite profiles compared to cancer-free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). CONCLUSIONS These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests.

Original languageEnglish (US)
Pages (from-to)1547-1560
Number of pages14
JournalProstate
Volume73
Issue number14
DOIs
StatePublished - Oct 2013

Fingerprint

Metabolomics
Prostate
Prostatic Neoplasms
Neoplasms
Sarcosine
Kynurenine
Nomograms
Neoplasm Grading
Seminal Vesicles
Polyamines
Prostatectomy
Tandem Mass Spectrometry
Routine Diagnostic Tests
Citric Acid
Liquid Chromatography
Biochemistry
NAD
Gas Chromatography-Mass Spectrometry
Carcinogenesis
Lymph Nodes

Keywords

  • clinical heterogeneity
  • diagnosis
  • metabolomics
  • prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

McDunn, J. E., Li, Z., Adam, K. P., Neri, B. P., Wolfert, R. L., Milburn, M. V., ... Wheeler, T. M. (2013). Metabolomic signatures of aggressive prostate cancer. Prostate, 73(14), 1547-1560. https://doi.org/10.1002/pros.22704

Metabolomic signatures of aggressive prostate cancer. / McDunn, Jonathan E.; Li, Zhen; Adam, Klaus Peter; Neri, Bruce P.; Wolfert, Robert L.; Milburn, Michael V.; Lotan, Yair; Wheeler, Thomas M.

In: Prostate, Vol. 73, No. 14, 10.2013, p. 1547-1560.

Research output: Contribution to journalArticle

McDunn, JE, Li, Z, Adam, KP, Neri, BP, Wolfert, RL, Milburn, MV, Lotan, Y & Wheeler, TM 2013, 'Metabolomic signatures of aggressive prostate cancer', Prostate, vol. 73, no. 14, pp. 1547-1560. https://doi.org/10.1002/pros.22704
McDunn JE, Li Z, Adam KP, Neri BP, Wolfert RL, Milburn MV et al. Metabolomic signatures of aggressive prostate cancer. Prostate. 2013 Oct;73(14):1547-1560. https://doi.org/10.1002/pros.22704
McDunn, Jonathan E. ; Li, Zhen ; Adam, Klaus Peter ; Neri, Bruce P. ; Wolfert, Robert L. ; Milburn, Michael V. ; Lotan, Yair ; Wheeler, Thomas M. / Metabolomic signatures of aggressive prostate cancer. In: Prostate. 2013 ; Vol. 73, No. 14. pp. 1547-1560.
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