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By Rebecca V. Snowden

Men whose urine contains a high concentration of a molecule called sarcosine appear to be more likely to have advanced prostate cancer, according to a study from University of Michigan researchers. While the finding is preliminary, the discovery could eventually lead to the development of a better tool for monitoring and treating prostate cancer.

"One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up overtreating our patients because physicians don't know which ones will be slow-growing. With this research, we have identified a potential marker for the aggressive tumors," says senior study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology and SP Hicks Endowed Professor of Pathology at the University of Michigan Medical School.

Researchers studied over 1000 metabolites (metabolites are small molecules related to cell growth) in nearly 300 tissue, blood, and urine samples taken from men with no signs of prostate cancer and those who were at different stages of the disease.

Says Chinnaiyan: "When we're looking at metabolites, we're looking several steps beyond genes and proteins. It allows us to look very deeply at some of the functions of cells and the biochemistry that occurs during cancer development."

They analyzed and profiled the metabolites using mass spectrometry and found 10 metabolites that appear to be elevated in men with advanced disease. One molecule in particular – sarcosine, a modified amino acid – appeared to be consistently elevated. In fact, sarcosine levels were 79% higher in the urine of those men. The scientists found that sarcosine levels were also higher among men who had had a positive biopsy, compared to men whose results came back negative.

Researchers were also able to better differentiate between men at different stages of prostate cancer using information about sarcosine levels than they were with the prostate-specific antigen test (PSA), currently the standard.

The hope is that one day the findings could lead to the development of a simple urine test that may help eliminate unnecessary biopsies – and help doctors better monitor their patients.

While the PSA test is a useful screening tool, it isn't foolproof: abnormal results of these tests don't always mean that cancer is present, and normal results don't mean that there is no cancer. Many men end up having prostate biopsies when there's no cancer present.

And because of an elevated PSA level, some men may be diagnosed with a prostate cancer that they would have never even known about otherwise and would never have caused any symptoms.

If results from the current study are validated by additional studies and a test is developed, many men could potentially avoid unnecessary treatment that often compromises quality-of-life.

"We could potentially monitor the metabolites in a prostate cancer sample to tell us which patients have the more aggressive disease that will progress on to metastasis," says Chinnaiyan. "We also believe that the findings may have therapeutic implications because one of the interesting findings in this particular study is that pathways that are involved in sarcosine metabolism appear to be involved in cancer invasiveness and prostate cancer aggressiveness in general."

"This could be a wonderful find, if it holds up," says Durado Brooks, MD, director of prostate and colorectal cancers at the American Cancer Society. "However, the results are preliminary at this point."

Citation: "Metabolic profiles delineate potential role for sarcosine in prostate cancer progression." Published in the February 12, 2009 issue of Nature. Corresponding author: Arul M. Chinnaiyan, MD, PhD, Michigan Center for Translational Pathology and University of Michigan Medical School.