BERKELEY, CA (UroToday.com) - Our work is focused on the development of a new prognostic test using a patient's own gene activity profile to provide a prognosis for the risk of progression following prostatectomy. A novel feature of our approach is to utilize the tissue of the stroma or microenvironment of tumor-bearing prostate tissue.
Considerable information has accumulated over the past 20 years that the microenvironment of tumors exhibits altered gene activity in response to the presence of tumor. In our first study of stroma of tumor-bearing patients published last year (Cancer Research, 71:2476-2487), we described stroma gene activity changes that could be used to diagnose the presence-of-tumor just from data from the stroma tissue. The profile was validated in over 300 independent cases. 
This taught us that indeed the stroma behaved as a constant source of information across many cases. In addition, factors secreted by tumors of different aggressiveness may affect stroma. Stroma is, therefore, a natural place to look for gene activity changes that signify indolent or aggressive tumor behavior. An additional major advantage of looking at stroma is that the stroma of tumor-bearing cancer patients exhibits very few genetic alterations, whereas tumors exhibit hundreds of DNA alterations such as point mutations, loss of heterozygosity (loss of one of the two copies of genes), deletions, insertions, and translocations. These changes are not the same in every patient and are not the same in all places within a single tumor. This is the so-called "polyclonal" problem of prostate cancer. As a result, different groups using different sources of tumor tissues have failed to observe a consistent set of genetic alterations that are generally usable as a test when studying only the tumor cells. In the present study, we identified that the activity of 15 genes as measured in stroma could predict whether the tumor was aggressive, that is relapsed after prostatectomy, or remained indolent, in which there was no further rise in the PSA marker for six years, about the limit of our follow-up period. As before, we also validated these findings.
The next step for creating a clinical test is to convert the array-based RNA measurements into a PCR test that is convenient for use in a CLIA lab using patient's biopsy blocks. One of the most urgent questions in urological practice is prognosis. Our test will provide a personal gene activity profile, and our university has filed a patent application and has licensed the intellectual property to a biotechnology company that is interested in developing the test. We hope to move quickly.
Written by:
Zhenyu Jia as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA USA
Expression changes in the stroma of prostate cancer predict subsequent relapse - Abstract
More Information about Beyond the Abstract