Researchers have identified a gene signature that is expected to help predict which low-risk prostate tumors will become lethal.

With prostate cancer screening becoming more widespread through prostate-specific antigen (PSA) testing, many new diagnoses involve tumors with low Gleason scores (most common prostate cancer cell grading scale), which require no treatment intervention, according to a research team led by Cory Abate-Shen, PhD, who is the Michael and Stella Chernow Professor of Urological Oncology at Columbia University Medical Center, New York, New York.  However, wrote the investigators in their report for Science Translational Medicine (2013;5:202ra122), distinguishing the many indolent tumors from the minority of those that will become aggressive and metastasize remains a major clinical challenge.

Now, Abate-Shen and her team have shown that prostate tumors with low Gleason scores can be classified into indolent or aggressive subgroups based on their expression of three genes associated with aging and senescence, the process that stops old cells from dividing. Cellular senescence is critical to tumor suppression in general and has been associated with benign prostate lesions.

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After identifying a 19-gene signature enriched in indolent prostate tumors, the researchers found that three particular genes together accurately predicted outcome of the low-Gleason-score tumors: FGFR1, PMP22, and CDKN1A. The three genes were highly expressed in tumors that remained low-risk, and underexpressed in tumors that became lethal.

In biopsy specimens from 43 patients who had been monitored for 10 years or more after receiving a diagnosis of low-risk prostate cancer as defined by Gleason score of 6 or lower as well as other measures, 14 tumors eventually developed into advanced prostate cancer. All 14 cases were correctly identified by the three-gene test.

As summarized in a statement from Science Translational Medicine, the results suggest that once developed into a diagnostic test, this gene signature could be a useful tool for guiding prostate cancer treatment.