Urine Test May Identify Aggressive Prostate Cancer Nick Mulcahy Information from Industry Assess clinically focused product information on Medscape. Click Here for Product Infosites – Information from Industry. February 12, 2009 — An experimental urine test is "at least as good" as the prostate-specific antigen (PSA) test for predicting which men have aggressive prostate cancer, according to a University of Michigan researcher who participated in a new study published online in the February 12 issue of Nature. The urine test, which assesses levels of prostate-cancer-specific metabolites, could eventually be added to PSA and other tools for monitoring prostate cancer progression, said study coauthor John Wei, MD, at a press briefing. Dr. Wei is an associate professor of urology at the University of Michigan Medical School, in Ann Arbor. However, the new study had a small sample, and the scientific approach to analyze metabolites as prostate cancer biomarkers needs further validation and development, he added. Nonetheless, Dr. Wei and his colleagues believe that 1 of the metabolites, sarcosine, has the potential to differentiate between benign prostate tissue and localized/metastatic prostate cancer. "One of the main clinical issues in prostate cancer is distinguishing between aggressive [and] indolent slow-growing disease," said senior author Arul Chinnaiyan, MD, PhD, during the press briefing. The inability to do so leads to "overtreatment," added Dr. Chinnaiyan, who is director of the Michigan Center for Translational Pathology, in Ann Arbor. In the new study, the researchers identified at least 10 prostate-cancer-specific metabolites. Notably, sarcosine was increased "most robustly in metastatic prostate cancer," in comparison with the others, they write. It was also elevated in locally advanced prostate cancer, but less so, added Dr. Chinnaiyan. Dr. Chinnaiyan's lab has also developed urine tests to screen for prostate cancer that are more accurate than PSA tests, as reported by Medscape Oncology. But the tests employ genetic biomarkers and are for screening, not monitoring, the disease. The new study is the first time that "metabolomics," which surveys the metabolite composition of cells and tissues, akin to the way genetics surveys their genetic composition, has been shown "to solve a real-world problem," said the researchers at the press briefing. Why Prostate-Cancer-Specific Metabolites? In the study, the investigators examined 1126 metabolites across 262 samples of tissue, blood, or urine associated with benign prostate tissue, early-stage prostate cancer, and metastatic prostate cancer. Of the metabolites that were present more often in prostate cancer than in the benign cells, sarcosine appeared to be the strongest indicator of advanced disease. Levels of sarcosine, an amino acid, were elevated in 79% of the metastatic prostate cancer samples and in 42% of the locally advanced cancer samples. Sarcosine was not found in the cancer-free samples. In the study, sarcosine was a better indicator of advancing aggressive disease than the PSA test, which both monitors and screens for prostate cancer. "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 the cells and the biochemistry that occurs during cancer development," added Dr. Chinnaiyan in a statement. The researchers also showed that adding sarcosine to cultures of benign prostate cells turned them into invasive cancer cells, suggesting that the molecule may have an important role in disease. "Components of the sarcosine pathway may have potential as biomarkers of prostate cancer prevention and serve as new avenues for therapeutic intervention," note the authors. The Future of Prostate Cancer Testing "Current biomarkers for detection or progression of prostate cancer are not as precise as we would like. Therefore, a more accurate indicator of cancer is of great interest," said Sudhir Srivastava, PhD, chief of the National Cancer Institute (NCI)'s Cancer Biomarkers Research Group, in a statement. "Sarcosine and some other select metabolites may be excellent indicators of cancer progression." The NCI Early Detection Research Network supported the study, but the Michigan researchers emphasized that their urine test is not a screening test. "We only examined sarcosine in the context of aggressive prostate cancer," noted Dr. Wei. "A lot more work has to be done before it can be used as a screening test." Sarcosine was detected in the urine, which makes researchers hopeful that a simple urine test could be used to monitor the disease. Dr. Wei imagined that the combination of the PSA test and new biomarkers, such as prostate-cancer-specific metabolites (including sarcosine and some of the others identified in the new study), will allow clinicians to eventually "individualize" the analysis of patients. "This may allow clinicians to determine — before biopsy — the severity of disease," he speculated. The study was funded by the National Cancer Institute Early Detection Research Network, National Institutes of Health, an MTTC grant, the Burroughs Welcome Foundation, and the Doris Duke Charitable Foundation. Nature. 2009.457:910-915, 799-800. Related Links News Urine Biomarker Test More Accurate in Detecting Prostate Cancer Than PSA Resource Centers Prostate Cancer Resource Center

New prostate cancer marker-Sarcosine

Survey of metabolites finds new prostate cancer marker

sarcosine in prostate cancer

February 11, 2009

Potential role for sarcosine in prostate cancer progression

A very interesting paper in Nature this week looked at a metabolite called sarcosine and how it's detection in urine may distinguish slow growing prostate cancers from aggressive ones. The paper, entitled "Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression", may well be a useful new marker in helping doctors decide when to stop 'watchful waiting' and treat prostate cancer patients more aggressively.

The researchers examined 1,126 metabolites from over 260 samples of blood, urine and tissue in benign prostate tissue, early stage prostate cancer and advanced or metastatic disease to enable them to map alterations in disease state.

Sarcosine molecule from: jchemed.chem.wisc.edu

They found 10 that were present more often in prostate cancer samples and one, sarcosine, appeared to offer the strongest indicator.

"... by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity."

Sarcosine is an amino acid and was found to be elevated in 79% of the metastatic prostate cancer samples and 42% of the early prostate cancer samples. None of the cancer-free samples had detectable levels of the metabolite.

So how does this happen? Is there an explanation for the phenomenon reported? The researchers went on to say that:

"Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway."

What was also interesting was the finding that:

"Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells."

In other words, they found a clear relationship between the sarcosine and the metastatic invasion. The study also found that sarcosine was a better indicator of advancing disease than the traditional measure, prostate specific antigen (PSA), which is currently used to monitor prostate cancer.

Sources:

Thanks to Prof Chris Beecher for kindly supplying a copy of the Nature reprint.

Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaeman Byun, Gilbert S. Omenn, Debashis Ghosh, Subramaniam Pennathur, Danny C. Alexander, Alvin Berger, Jeffrey R. Shuster, John T. Wei, Sooryanarayana Varambally, Christopher Beecher, Arul M. Chinnaiyan (2009). Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression Nature, 457 (7231), 910-914 DOI: 10.1038/nature07762

Can a Urine Test Detect Deadly Prostate Cancer? - TIME

Can a Urine Test Detect Deadly Prostate Cancer? - TIME