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SPINK1 Implicated in Prostate Cancer Aggressiveness

Oncogene a predictor of cancer recurrence

FRIDAY, June 13 (HealthDay News) -- The oncogene SPINK1 is a biomarker detectable in urine that's associated with prostate cancer aggressiveness, with outlier expression identified only in a subset of ETS-negative cancers, researchers report in the June issue of Cancer Cell.

Scott A. Tomlins, of the University of Michigan Medical School in Ann Arbor, and colleagues conducted an analysis of nine prostate cancer profiling studies to prioritize candidate oncogenes, looking for those with outlier profiles. SPINK1 (serine peptidase inhibitor, Kazal type 1) showed outlier expression in only 2.9 percent of benign prostate samples and 14.9 percent of localized cancers. Further investigation found that SPINK1 expression and ETS fusion status are mutually exclusive.

After analyzing data sets from prostate cancer cohorts, the researchers found that SPINK1 outlier status was a significant predictor of recurrence independently of other clinical parameters. SPINK1 outlier expression could also be detected non-invasively in urine. In addition, using the aggressive 22RV1 cell line, they found that SPINK1 knockdown attenuated the invasiveness of the cells.

"We provide evidence that SPINK1 outlier expression defines an aggressive molecular subtype of prostate cancer (about 10 percent of cases) not attributable to known gene fusion events. We hypothesize that the molecular lesion or lesions that initially drive ETS-negative tumors, which are presently unclear, may predispose to activation of SPINK1 expression later in prostate cancer progression. Additionally, SPINK1-positive tumors may arise from a different prostate progenitor cell type than ETS-positive tumors, and SPINK1 expression may be a marker of this cell type," the authors write.

Abstract
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