Biomarker, potential drug target identified for prostate cancer

NEW YORK (Reuters Health) - The level of the amino acid derivative sarcosine in urine appears to be a better indicator of prostate cancer than prostate specific antigen (PSA), according to a report in the February 12 issue of Nature.

Furthermore, sarcosine's role in cancer progression suggests that the metabolite may also represent a novel drug target.

"Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression," writes the research team, led by Dr. Arul M. Chinnaiyan at the University of Michigan Medical School in Ann Arbor.

Using liquid and gas chromatography coupled with mass spectrometry, the team determined metabolite profiles for 42 biopsy samples (16 from benign adjacent prostate tissue, 12 from clinically localized prostate cancer and 14 from metastatic prostate cancer), as well as for plasma and urine specimens from 59 biopsy-positive cancer patients and 51 biopsy-negative control individuals.

According to the researchers, "Six metabolites including sarcosine, uracil, kynurenine, glycerol-3-phosphate, leucine and proline were significantly increased on disease progression from benign to localized prostate cancer to metastatic prostate cancer."

They chose to further evaluate sarcosine, an N-methyl derivative of glycine, based on its complete absence in benign tissue, its differential expression in localized versus metastasized cancer, as well as the ability to detect sarcosine levels noninvasively in urine.

In cultured prostate cancer cell lines, sarcosine levels correlated with cell invasiveness, the report indicates.

"Remarkably," Dr. Chinnaiyan's group states, "the mere addition of exogenous sarcosine imparted an invasive phenotype to benign prostate epithelial cells." Moreover, altering levels of the enzymes that regulate sarcosine metabolism changed the invasiveness of benign and malignant prostate cells.

"Components of the sarcosine pathway may have potential as biomarkers of prostate cancer progression and serve as new avenues for therapeutic intervention," they add.

The researchers also observed that sarcosine performed better than PSA in the 2-10 ng/mL range in differentiating benign and malignant disease state, leading them to conclude that "sarcosine may have the potential to identify patients with modestly increased PSA that are likely to have a positive prostate biopsy."

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