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Metabolomics Study Uncovers Prostate Cancer Biomarker

NEW YORK (GenomeWeb News) – In a study appearing online today in Nature, a team of American researchers reported that they have identified a biomarker for prostate cancer progression and metastasis during a metabolomic study of more than 250 clinical samples.

Although the methods for diagnosing prostate cancer are very effective, predicting disease progression remains challenging. In the new study, senior author Arul Chinnaiyan, a researcher at the University of Michigan and director of the Michigan Center for Translational Pathology, led a team of researchers using metabolomics to try to find new metabolites linked to prostate cancer progression.

The researchers found that metabolomics could help them distinguish between benign prostate disease, localized prostate cancer, and metastatic prostate cancer. In the process, they identified a metabolite called sarcosine, a derivative of the amino acid glycine, whose levels seem to increase with cancer progression and metastasis.

"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 tumors will be slow growing," Chinnaiyan said in a statement. "With this research, we have identified a potential marker for the aggressive tumors."

The researchers used high-throughput liquid and gas chromatography-based mass spectrometry to assess 1,126 metabolites from 262 clinical samples — 42 tissues, 110 urine samples, and 110 blood plasma samples — from both prostate cancer biopsy-positive and –negative individuals.

The team detected dozens of metabolites in localized and metastatic prostate cancer tissue samples that were not found in benign prostate tissue samples. Meanwhile, six metabolites were significantly elevated during progression from a benign condition or localized prostate cancer to metastatic prostate cancer.

The results may help researchers identify biological and biochemical processes underlying prostate cancer development and progression. And, the team noted, metabolites linked to disease progression could eventually become useful biomarkers.

In particular, the researchers focused on sarcosine, a compound absent from cancer-free samples that increases progressively during the transition from benign prostate tissue to localized prostate cancer to metastatic cancer. They detected high sarcosine levels in 79 percent of metastatic prostate cancer samples and about 42 percent of early-stage cancer samples.

When the team looked at prostate cancer cell lines, they found a similar link between sarcosine and prostate cancer progression. For instance, knocking down the enzyme that converts glycine to sarcosine curbed prostate cancer's invasiveness, while adding sarcosine or knocking down the enzyme that degrades it prompted benign prostate epithelial cells to take on an invasive phenotype.

Overall, the researchers found that urine sarcosine levels had a modest predictive value for prostate cancer progression. But for samples that were difficult to distinguish by traditional prostate specific antigen testing, the sarcosine levels were better at distinguishing different prostate cancer patients.

And since the metabolite was detected in urine, the researchers expressed enthusiasm about the possibility of eventually developing an easy clinical test for prostate cancer progression and metastasis.

"Current biomarkers for detection of progression of prostate cancer are not as precise as we would like. Therefore, a more accurate indicator of cancer is of great interest," Sudhir Srivastava, head of the National Cancer Institute's Cancer Biomarkers Research Group, who was not involved in the study, said in a statement. "Sarcosine and some other select metabolites may be excellent indicators of cancer progression."

Still, Chinnaiyan noted that more research will be necessary to expand on the findings in the new paper. "Components of the sarcosine pathway could serve as novel avenues for therapeutic intervention," he said. "Our next step will be to confirm these findings in a greater number of specimens and to have our results validated by other laboratories."

In a News and Views article also online today in Nature, Columbia University urology and pathology researcher Cory Abate-Shen and Columbia University genetics and development researcher Michael Shen noted that more research is necessary to reconcile the role of sarcosine in cancer, since a previous study demonstrated that mice lacking the enzyme that converts glycine to sarcosine were more likely to develop liver cancer.

Even so, the duo said evaluating the levels of sarcosine or other metabolites identified in the new study could prove useful for diagnosing prostate cancer, in combination with existing tests. "At present, the greatest value of metabolomic approaches seems to be for the development of non-invasive screening procedures that can be used for effective cancer diagnosis and prognosis," Abate-Shen and Shen wrote.

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