Metabolomics and its Application to the Development of Clinical Laboratory Tests for Prostate Cancer.
BACKGROUND
There is a critical need to develop clinical laboratory assays that provide risk assessment for men at elevated risk for prostate cancer, and once diagnosed, could further identify those men with clinically significant disease.


METHODS
Recent advancements in analytical instrumentation have enabled mass spectrometry-based metabolomics methodologies. Further advancements in chromatographic techniques have facilitated high throughput, quantitative assays for a broad spectrum of biochemicals.


RESULTS
Screening metabolomics techniques have been applied to biospecimens from large cohorts of men comparing those individuals with prostate cancer to those with no evidence of malignancy. Work beginning in tissues has identified biochemical profiles that correlate with disease and disease severity, including tumor grade and stage. Some of these metabolic abnormalities, such as dramatic elevations in sarcosine, have been found to translate into biological fluids, especially blood and urine, which can be sampled in a minimally invasive manner.


CONCLUSIONS
The differential abundances of these tumor-associated metabolites have been found to improve the performance of clinical prognostic/diagnostic tools.


CONCLUSIONS
The outlook is bright for metabolomic technology to address clinical diagnostic needs for prostate cancer patient management. Early validation of specific clinical tests provides a preview of further successes in this area. Metabolomics has shown its utility to complement and augment traditional clinical approaches as well as emerging genomic, transcriptomic and proteomic methodologies, and is expected to play a key role in the precision medicine-based management of the prostate cancer patient.
Metabolon Inc.
Jonathan E
JE
McDunn
Metabolon Inc.
Steven M
SM
Stirdivant
Metabolon Inc.
Lisa A
LA
Ford
Metabolon Inc.
Robert L
RL
Wolfert
Nature. 2009 Feb 12;457(7231):910-4
19212411
Prostate Cancer Prostatic Dis. 2011 Jun;14(2):166-72
21321584
Cancer Biol Ther. 2011 Jan 15;11(2):150-6
21191189
Prostate. 1991;18(1):25-46
1987578
Carcinogenesis. 2013 Oct;34(10):2281-5
23698636
Nat Rev Cancer. 2011 Feb;11(2):85-95
21258394
Cancer Biol Ther. 2010 Sep 15;10 (6):537-42
20861671
EMBO J. 2011 May 20;30(13):2719-33
21602788
Nat Rev Urol. 2010 Dec;7(12):668-80
21060342
Urol Oncol. 2011 Sep-Oct;29(5):572-81
21930089
Magn Reson Med. 2006 Jun;55(6):1257-64
16685733
Curr Opin Endocrinol Diabetes Obes. 2013 Jun;20(3):204-9
23609043
Nat Rev Cancer. 2011 May;11(5):325-37
21508971
Prostate. 2013 Oct;73(14):1547-60
23824564
Clin Cancer Res. 2009 Jan 15;15(2):431-40
19147747
Neoplasia. 2013 May;15(5):491-501
23633921
Int J Cancer. 2014 Jan 1;134(1):197-206
23797698
PLoS One. 2010 Dec 03;5(12):e14175
21151972
J Clin Oncol. 2013 May 20;31(15):1866-73
23589550
Nat Rev Cancer. 2010 Mar;10(3):181-93
20168319
Prostate. 2011 May 15;71(7):700-10
20957673
J Inherit Metab Dis. 1990;13(3):321-4
2122093
Curr Opin Pharmacol. 2012 Oct;12(5):623-8
22858243
BJU Int. 2013 Jan;111(1):22-9
22834909
J Urol. 2011 Feb;185(2):706-11
21168877
J Urol. 2003 Feb;169(2):517-23
12544300
Mod Pathol. 2011 Sep;24(9):1272-80
21572396
J Neural Transm (Vienna). 2012 Feb;119(2):197-209
21744051
Anal Chim Acta. 2011 Nov 30;707(1-2):197-203
22027139
CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
22237781
Korean J Urol. 2011 Feb;52(2):79-89
21379423
J Sep Sci. 2011 Dec;34(24):3619-21
22009695
Prostate. 1998 Jun 1;35(4):285-96
9609552
Prostate. 2008 May 1;68(6):620-8
18213632
Cancer Cell. 2012 Mar 20;21(3):297-308
22439925
Acta Paediatr Suppl. 1999 Dec;88(432):45-7
10626577
Magn Reson Med. 2003 Nov;50(5):944-54
14587005
Biosci Rep. 2013 Sep 17;33(5):null
23883094
J Clin Oncol. 2011 Sep 20;29(27):3669-76
21825257
Magn Reson Med. 2008 Jul;60(1):33-40
18581409
Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):e781-6
22331001
Mol Med. 1996 May;2(3):274-82
8784780
Ann Intern Med. 2011 Dec 6;155(11):762-71
21984740
Sci Transl Med. 2012 Mar 28;4(127):127rv3
22461644
Clin Cancer Res. 2012 Jul 1;18(13):3677-85
22589396
Prostate Suppl. 1996;6:36-44
8630228
Clin Transl Sci. 2012 Jun;5(3):285-8
22686208
PLoS One. 2012;7(11):e48889
23152813