Published online 11 February 2009 | Nature | doi:10.1038/news.2009.94

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Prostate cancer marker found in urine

A simple urine test for sarcosine could be used to detect cancer.

Prostate cancer cellThe findings could lead to less invasive prostate cancer tests.Nina Lampen / Science Photo Library

The concentration of a small molecule found in urine could reveal how advanced a patient's prostate cancer is. The discovery could lead to simple, non-invasive tests for men who have the disease and might help avoid the need for biopsies.

Researchers identified the molecule, a derivative of the amino acid glycine called sarcosine, after close inspection of all the metabolites found in 262 samples from prostate cancer patients — all of whom had different stages of the disease — including benign cells to aggressive metastasized cancers able to spread to other organs. Metabolites are the substances involved in or produced by the chemical reactions that take place in the body, and the concentrations of these chemicals can change as cancer progresses.

Christopher Beecher at the University of Michigan in Ann Arbor, led the metabolomic analysis. Generally, researchers screen only for metabolites that they think might be affected during a disease. But, using mass spectrometry, Beecher's team looked at all the metabolites present in their samples. "We would never have expected to see sarcosine, nor would we have expected to look for it," he says.

According to the charity Cancer Research UK, more than 670,000 men are diagnosed worldwide with prostate cancer each year. Survival rates vary due to different screening and treatment policies or but in the United Kingdom around 30% of men die within 5 years of diagnosis.

“We could actually detect this metabolite non-invasively.”

Arul Chinnaiyan
niversity of Michigan

At the moment, prostate cancer is diagnosed and monitored by testing for high concentrations of prostate-specific antigen (PSA), often followed by a biopsy to determine whether the cancer is aggressive or slow-growing.

If further testing and validation confirm the new results, sarcosine concentrations in urine could be used to predict the aggressiveness of a cancer.

"We could actually detect this metabolite non-invasively in the urine of men with prostate cancer," says Arul Chinnaiyan, also at the University of Michigan, who led efforts to look at how sarcosine interacts with cancer cells.

Moving target

Beecher's team found that at least six metabolites showed up in higher concentrations in the samples of metastatic cancer than in those of any other stage of the disease. Sarcosine was present in especially high concentrations.

Chinnaiyan and his colleagues then identified the enzymes that make and degrade sarcosine and altered the genes that controlled the production of these enzymes in cells grown in culture. The research is published in Nature1.

Sarcosine levelsSarcosine concentrations in benign cells (left); localised prostate cancer (centre) and metastatic prostate cancer (right).Nature

"Any time they did anything that increased production [of sarcosine], the cells became highly mobile," says Beecher. The cells started to move so much they could get themselves into a sample of gelatine under their own force — a behaviour that cancerous cells also show. Simply adding sarcosine to benign prostate cells made them behave like cancerous cells.

The implication is that sarcosine is not only an indicator of how aggressive a cancer has become, it also has a role in making cells move and become aggressively cancerous.

The study could also provide new targets for treatments. "Not only have they got a marker that has a fundamental role in invasion and metastasis, the molecule itself is regulated by systems that have been directly implicated in prostate cancer," says Malcolm Mason, Cancer Research UK's prostate-cancer expert from Cardiff University, UK. "There's enough to say that [sarcosine] should be looked at as a possible drug target."

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But Mason adds that the study needs to be validated further, and cautions that sarcosine is unlikely to be the basis of a widespread screening programme. Several large clinical trials for screening for the disease are under way, in Europe, he says, and until these results are in, it is hard to say what role sarcosine urine tests will have. They are most likely to be used to differentiate between men who need biopsies and those who don't. "This isn't a simple urine test that you can do at the chemist's," says Mason.

Beecher, however, has high hopes that sarcosine will find a place in prostate-cancer tests, and possibly even replace current tests. "This may actually be superior to PSA," he says. Other metabolites identified in the study could also be added to a test as "a panel of metabolites that we could monitor", says Chinnaiyan.

Beecher now wants to use his methods to look for biomarkers for other diseases. "We will be looking at every disease that we can get our hand on," he says. 

  • References

    1. Sreekumar, A. et al. Nature 457, 910–914 (2009).
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