Author(s): Chan SW, Nguyen PN, Violette P, Brimo F, Taguchi Y,
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Abstract We explore noninvasive clinical applications of multiple disease-specific fusion markers recently discovered in prostate cancer to predict the risk of cancer occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate-specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled for this study. Prospectively collected urine was blind coded for laboratory tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS fusion markers with a sensitive quantitative PCR platform. The pathology reported 39 biopsy-positive cases from 92 patients (42.4\%). In urine test, 10 unique combinations of fusion types were detected in 32 of 92 (34.8\%) prebiopsy samples. A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified with a sensitivity of 51.3\% and an odds ratio of 10.1 in detecting cancer on biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3 and serum PSA, a regression model was developed to predict biopsy outcomes with an overall accuracy of 77\%. Moreover, the overexpression of Fx (III, IV, or ETS) was shown to be an independent predictor to the high-grade cancer, with a predictive accuracy of 80\% when coupled with PSA density. The individualized risk scores further stratified a high-risk group that is composed of 92\% high-grade cancers and a low-risk group that harbors mainly clinically insignificant cancers. In conclusion, we have identified a novel combination of fusion types very specific to the clinically significant prostate cancer and developed effective regression models to predict biopsy outcomes and aggressive cancers at diagnosis.
This article was published in Cancer Med
and referenced in Medicinal Chemistry