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Patterns of Gene Expression May Help Predict the Course of Prostate Cancer

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Image: MARK RUBIN/University of Michigan Medical School

For almost 15 years, doctors have had to rely on the Prostate Specific Antigen (PSA) test as the best available method to screen men for prostate cancer. But within another three to five years, far more accurate diagnostic tests will most likely emerge, researchers at the University of Michigan Medical School now say. They recently completed an extensive analysis of more than 200 genes and gene fragments, and found distinct patterns of gene expression associated with the timing and severity of the disease. The scientists describe their findings in today's issue of Nature.

"Our study has important applications in the diagnosis, prognosis and treatment of prostate cancer," co-author Mark Rubin says. "The ultimate goal is to help physicians determine which patients need immediate, aggressive treatment and which can be watched and treated conservatively."

Whereas previous studies examined prostate cancer genes one at a time, this research engaged more than 80 DNA microarrays in tandem to assess the activities of thousands of genes at once. The scientists tested different types of prostate tissue taken from 50 men. The samples included normal prostate tissue from men with and without prostate cancer (left image), tissue with benign changes, localized prostate cancer (right image) and aggressive, metastatic cancer. The approach turned up some well-known cancer genes but also identified other genes that were not known to be involved in the disease.

In particular, the researchers found that the protein made by a gene called hepsin appeared at the highest levels in prostate tissue just before it turned cancerous. And the pim-1-gene product¿a protein known to cause cancer¿was highly expressed in prostate cancer. Both protein levels, the researchers say, correlated to a patient's prognosis and thus might prove to be important clinical biomarkers. Now the team hopes to work out what the various genes actually do. "This paper will generate a great deal of work for researchers in many laboratories," concludes Arul Chinnaiyan, who directed the study.

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