Simple Urine Test May Reveal the Aggressiveness of
Your Prostate Cancer
Sarcosine is better indicator of advancing disease
than traditional prostate specific antigen test (PSA); it is detected in
urine, researchers hopeful simple urine test can be used
Feb. 12, 2009 Prostate cancer will be discovered
in 186,320 American men this year, mostly senior citizens, and each case
launches a myriad of decisions for the patient. The first question may
be, How bad is the cancer. That has been tough to answer. But, today,
scientists report they have discovered a way to determine how aggressive
the cancer is.
"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.
In experiments reported in todays Nature,
the scientists identified 10 metabolites that become more abundant in
prostate cells as cancer progresses. Their studies showed that one of
these chemicals, sarcosine, helps prostate cancer cells invade
surrounding tissue.
The finding by researchers from the
University of Michigan Comprehensive Cancer Center could lead to a
simple test that would help doctors determine which prostate cancers are
slow-growing and which require immediate, aggressive treatment.
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 were looking at metabolites, were 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.
An important next step, Chinnaiyan said, will be to
do similar experiments on the other nine potential biomarkers they
identified in this study. For reliable diagnosis of aggressive disease,
he said, "we need to have panels, not just rely on a single metabolite."
Prostate cancer is expected to kill 28,660
Americans this year, according to the
American Cancer Society
Background Information and Links
Prostate Cancer
The prostate is the gland below a man's
bladder that produces fluid for semen. Prostate cancer is the
third most common cause of death from cancer in men of all ages.
It is rare in men younger than 40.
Levels of a substance called prostate
specific antigen (PSA) is often high in men with prostate
cancer. However, PSA can also be high with other
prostate conditions. Since the PSA test became common, most
prostate cancers are found before they cause symptoms. Symptoms
of prostate cancer may include
>> Problems passing urine, such as pain,
difficulty starting or stopping the stream, or dribbling
>> Low back pain
>> Pain with ejaculation
Prostate cancer treatment often depends
on the stage of the cancer. How fast the cancer grows and how
different it is from surrounding tissue helps determine the
stage. Treatment may include surgery, radiation therapy,
chemotherapy or control of hormones that affect the cancer.
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.
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
