Researchers in the US have found a new marker of the aggressiveness of prostate cancer that is detectable in the urine of men with the malignancy. Sreekumar et al. discovered that levels of sarcosine, a common amino acid found in many biological tissues, are higher in invasive prostate cancers than in benign cancers and are detectable in the urine of affected men.
Currently, prostate cancer is detected by measuring blood levels of a marker called prostate specific antigen (PSA). The diagnosis is then confirmed by taking a tissue sample (biopsy) from the prostate using a fine needle – an uncomfortable and undignified process – and examining it under a microscope.
If further trials confirm that sarcosine levels in the urine do reflect how advanced a prostate cancer is, measurement of this marker could be used as a noninvasive way to predict the aggressiveness of a cancer and thus a patient’s prognosis.
In this study, the authors recorded all the metabolites (low molecular weight molecules produced by cells) found in samples from patients with various stages of prostate cancer, ranging from benign cancer to advanced metastatic cancer. In total, 1,126 metabolites in 262 clinical samples related to prostate cancer were profiled. The authors then compared the metabolites found in the various types of tumor tissues in order to unearth ‘molecular signatures’ that distinguished the different stages of prostate cancer.
In total, 87 metabolites that distinguished prostate cancer from benign prostate tissue were found, and the levels of six of these metabolites were even higher in metastatic cancer than in any other stage of disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was highly increased in metastatic samples and, importantly, was undetectable in the benign samples.
The authors then tested out what happened when they eliminated the enzyme glycine-N-methyl transferase, which is crucial for the production of sarcosine from its precursor glycine. The invasive properties of prostate cancer cells in culture were attenuated when this enzyme, and thus sarcosine, was absent. Addition of sarcosine to benign prostate epithelial cells or knockdown of the enzyme that is responsible for sarcosine degradation caused noncancerous cells to become invasive. Taken together, these findings suggest that not only is sarcosine a marker of cancer aggressiveness, it also has a role in endowing a cancer with malignant properties. Components of the sarcosine pathway may thus serve as new targets in the development of drugs that combat prostate cancer metastasis.
Lastly, the authors measured levels of sarcosine in urine specimens from individuals who had been definitively diagnosed with prostate cancer on the basis of PSA levels and prostate biopsy and compared these results with those from individuals who were biopsy negative. Levels of sarcosine were significantly higher in the urine of men with prostate cancer than in those without, confirming that measurement of sarcosine in the urine may act as an indicator of prostate cancer.
Senior study author Dr Arul Chinnaiyan told The Independent: “One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up over treating our patients because physicians don’t know which tumours will be slow-growing. With this research, we have identified a potential marker for the aggressive tumours.”
Sreekumar A et al. (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression Nature 457 (7231): 910-914 DOI: 10.1038/nature07762