Researchers Discover Metabolite Linked To Aggressive Prostate Cancer

Researchers from the University of Michigan Comprehensive Cancer Center have identified a panel of small molecules, or metabolites, that appear to indicate aggressive prostate cancer.

The finding could lead to a simple test that would help doctors determine which prostate cancers are slow-growing and which require immediate, aggressive treatment.

Results of the study appear in the Feb. 12 issue of Nature.

"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 tumors will be slow-growing. With this research, we have identified a potential marker for the aggressive tumors," says senior study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at the U-M Medical School.

The researchers looked at 1,126 metabolites across 262 samples of tissue, blood or urine associated with benign prostate tissue, early stage prostate cancer and advanced, or metastatic, prostate cancer. They mapped the alterations in metabolites and identified about 10 that were present more often in prostate cancer than in the benign cells and were present most often in the advanced cancer samples.

"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," says Chinnaiyan, a Howard Hughes Medical Institute investigator.

One metabolite in particular, sarcosine, appeared to be one of the strongest indicators of advanced disease. Levels of sarcosine, an amino acid, were elevated in 79 percent of the metastatic prostate cancer samples and in 42 percent of the early stage cancer samples. None of the cancer-free samples had detectable levels of sarcosine.

In the study, sarcosine was a better indicator of advancing disease than the traditional prostate specific antigen, or PSA, test that is currently used to monitor or screen for prostate cancer. Sarcosine was detected in the urine, which has researchers hopeful that a simple urine test could be used.

In addition, the researchers found that sarcosine is involved in the same pathways that are linked to cancer invasiveness. This suggests sarcosine as a potential target for future drug development.

"This research gets at characterizing the chemical complexity of a sample of cancer progression. In the future, this science will drive how doctors make treatment recommendations for their patients," says study author Christopher Beecher, Ph.D., professor of pathology at the U-M Medical School.

Results are preliminary at this point and will need years of further testing and development before this technology would be available for patients.

Prostate cancer statistics: 186,320 Americans will be diagnosed with prostate cancer this year and 28,660 will die from the disease, according to the American Cancer Society.

Additional authors: From the University of Michigan: 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, Jaemun Byun, Gilbert S. Omenn, Subramaniam Pennathur, John T. Wei and Sooryanarayana Varambally. From Metabolon Inc.: Danny C. Alexander, Alvin Berger and Jeffrey R. Shuster. From Penn State University: Debashis Ghosh.

Funding: National Cancer Institute Early Detection Research Network, National Institutes of Health, an MTTC grant, the Burroughs Wellcome Foundation, and the Doris Duke Charitable Foundation

Disclosure: The University of Michigan has exclusively licensed all pending patents covering this technology to Metabolon, a company with expertise in discovering biomarkers using metabolomics. Beecher, Alexander, Shuster and Chinnaiyan own equity in Metabolon and Chinnaiyan serves on its Scientific Advisory Board. Beecher is a previous employee of Metabolon.

Reference: Nature, Vol. 457, No. 7231, pp. 910-915, Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression