"This is good news in an area where our ability to diagnose and predict has previously been less than stellar," said Krishna Donkena, Ph.D., Mayo Clinic urologic researcher. "Our only tool is the PSA test, which has little predictive value. These findings move us much closer to a more accurate test."
The search to identify biomarkers that can be translated into affordable and effective medical tests can be complicated. Prostate cancer causes differential expression of hundreds of different genes, each potentially an indicator of whether a man may get the disease, or already has it. They also may be used to provide information on the development of the cancer, without the need for a painful tumor biopsy.
When seeking to narrow their search to a manageable level, the researchers analyzed 32 cancerous and eight benign patient-tissue samples using genome microarrays representing 33,000 human genes. The information they gleaned from this analysis allowed them to identify 624 differentially-expressed genes between cancerous and benign tissue. They validated these findings in the original 40 tissue samples as well as in 32 additional samples (20 cancerous, 12 benign). The results showed eight genes with significant under-expression and three with significant over-expression, strongly implicating them in prostate cancer development and progression.
Over the years, research has shown that DNA methylation is commonly linked to the development and progression of cancers. This epi-genetic alteration results in silencing or seriously inhibiting gene expression, which in turn lessens the body’s ability to defend against cancer. Current research has not done enough to discover ways to convert this information into a useful medical test, in large part due to the limited number of genes that have been thoroughly studied, and their insufficient sensitivity and specificity (probability of getting a true positive or true negative) for prostate cancer detection.
Dr. Donkena’s team looked at 62 cancerous and 36 benign tissue samples to assess the degree of methylation in the three previously identified under-expressed genes, comparing two known methylated genes. They determined that one gene, PDLIM4, had hypermethylation that could serve as an effective sensitivity marker, accurately detecting prostate cancer 95 percent of the time. The researchers further determined that the combined measurement of a previously known gene, GSTP1, and PDLIM4 improved the detection rate to 98 percent.
Prostate cancer is the second leading cause of cancer death for men in the United States, exceeded only by lung cancer. The sooner a cancer can be diagnosed, the better treatment outcomes will be, so Dr. Donkena and her colleagues are constantly looking for ways to predict who will get prostate cancer, as well as to find better ways to diagnose early or even prevent this disabling and often fatal disease. "We hope that in addition to being a valuable diagnostic and prognostic tool, our discoveries about these genes will help us develop new treatments for prostate cancer," she said.
Other Mayo researchers involved in this study include Karla Ballman, Ph.D.; Bruce Morlan; John Cheville, M.D.; Roxann Neumann; Michael Lieber, M.D.; Donald Tindall, Ph.D.; and Charles Young, Ph.D.
Elizabeth Zimmermann | EurekAlert!
WPI team grows heart tissue on spinach leaves
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Inactivate vaccines faster and more effectively using electron beams
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Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
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Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
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In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
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