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Researchers find better prostate cancer indicators

ROCHESTER, Minn. -- Researchers at Mayo Clinic have narrowed the search for effective prostate cancer biomarkers (genetic variations that point to a specific disease or condition), identifying changes in the expression of genes of the whole genome closely correlated to prostate cancer development and progression. They also showed that DNA hypermethylation (DNA modification without changing sequence) plays a significant role in these processes. Results of their study were published in the Feb. 15 issue of Clinical Cancer Research.

"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
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