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Abstract
Metabolomic profiling offers a powerful methodology for understanding the perturbations of biochemical systems occurring during a disease process. During neoplastic transformation, prostate cells undergo metabolic reprogramming to satisfy the demands of growth and proliferation. An early event in prostate cell transformation is the loss of capacity to accumulate zinc. This change is associated with a higher energy efficiency and increased lipid biosynthesis for cellular proliferation, membrane formation and cell signaling. Moreover, recent studies have shown that sarcosine, an N-methyl derivative of glycine, was significantly increased during disease progression from normal to localized to metastatic prostate cancer. Mapping the metabolomic profiles to their respective biochemical pathways showed an upregulation of androgen-induced protein synthesis, an increased amino acid metabolism and a perturbation of nitrogen breakdown pathways, along with high total choline-containing compounds and phosphocholine levels. In this review, the role of emerging biomarkers is summarized, based on the current understanding of the prostate cancer metabolome.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Prostate cancer (PCa) is the most common male malignancy. Recent estimates have calculated that in 2015, 220,800 new cases will be diagnosed and 27,540 patients will die of PCa in the USA.
Normal prostate cells have a particular metabolic profile characterized by an increased production of citrate and polyamines that are components of the prostatic fluid.
In PCa, the normal citrate-producing cells are metabolically transformed into citrate-oxidizing cells that lose the ability to accumulate zinc.
The PCa metabolome is characterized by an increased amino acid metabolism and a perturbation of nitrogen breakdown pathways, along with high total choline-containing compounds and phosphocholine levels.
Sarcosine, an N-methyl derivative of glycine, was identified as a metabolite that shows a progressive increase in benign, through localized, to metastatic PCa.
Androgens have an important role in regulating the PCa amino acid metabolism, and in altering the methylation potential, in accordance with the increased expression of methyltransferases like EZH2.
A significantly enriched UDP-glucuronosyltransferase activity, as well as sucrose metabolism and pentose/glucuronate interconversions, has been described in castration-resistant disease.