Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

The prostate has long been known to exhibit unique metabolite profiles. In the last decade, advances in nuclear magnetic resonance spectroscopy and mass spectrometry have been applied toward identifying metabolic alterations in prostate cancer that may provide clinically useful biomarkers. As with genomics and proteomics, advances in technology and bioinformatics have led to the application of metabolomic profiling to prostate cancer—the high throughput evaluation of a large complement of metabolites in the prostate and how they are altered by disease perturbations. Recently, high profile publications have drawn attention to the potential of metabolomic analysis to identify biomarkers for early detection or disease progression from readily accessible body fluids as well as tissue specimens from biopsy and surgery.

Worldwide, the number of prostate cancer cases is approaching one million, and it is the sixth leading cause of cancer deaths in men. Both incidence and mortality are increasing in many traditionally low risk countries in Asia, and Central and Eastern Europe. Testing with serum prostate specific antigen has contributed to decreases in prostate cancer mortality in many developed countries, but the test and the diagnostic paradigm suffer from a number of problems, including low specificity of prostate specific antigen, inability to specify a cut-point below which cancer is unlikely, non-trivial false-negative rate for prostate biopsy, and over-diagnosis and over-treatment of relatively indolent tumors with low potential for morbidity or death if left untreated. For men diagnosed with prostate cancer, a number of algorithms primarily based on tumor pathology and prostate specific antigen are available to predict the likely clinical outcome. Although these prediction tools generally work well, there is still significant variability in outcomes for men at both the low and high end of the risk spectrum. Although distinct metabolic characteristics of the prostate have long been known, global metabolomic profiling of prostate cancer is at an early stage.

Studies of the metabolic alterations associated with prostate cancer have demonstrated characteristic decreases in citrate and polyamines, and increases in cholines, glycerophospholipids, lactate, and components of a number of pathways of amino acid metabolism. Results for sarcosine have been prominent but inconsistent. However, it is likely that inconsistent findings are not unique to sarcosine. Rather, the attention given to sarcosine has resulted in reports of validation efforts focused on this molecule, whereas reports from other metabolomic profiling studies have focused on discovery and have not emphasized null associations. Metabolite profiles with potential relevance to prostate cancer biology have been identified in tissue, bone, urine, expressed prostatic fluid, and plasma, and have correlated with clinical progression as well as established prognostic attributes. Given the relatively low cost of metabolomic profiling compared with the other ‘omics’ disciplines, and the parallel advances being made in molecular magnetic resonance imaging, metabolomics has great potential for application to detection of clinically significant disease and monitoring disease progression, in both the active surveillance and post-treatment settings. In addition, because of their functional significance, metabolomic biomarkers or profiles hold particular promise for addressing one of the current challenges to personalized medicine: co-development of targeted therapeutics and companion diagnostics.

Source References:

http://www.ncbi.nlm.nih.gov/pubmed/21930089

http://people.ucalgary.ca/~adeleon/paper_prostate.pdf

http://www.ctsi.ufl.edu/wp-content/uploads/2012/06/DeFeo-2011-A-decade-in-prostate.pdf

http://www.fasebj.org/cgi/content/meeting_abstract/21/6/A768-c

http://onlinelibrary.wiley.com/doi/10.1002/pros.22704/abstract

http://dept.stat.lsa.umich.edu/~gmichail/journal.pone.0021417.pdf