UNASSIGNED: 194 Background: With the introduction of PSA testing, the problem of over-treatment emerged in @entity263 . Only a small subset of @entity263 @entity1 will require more intensive adjuvant therapy. There is currently no biomarker that can predict disease @entity146 at the time of surgery. METHODS: We analyzed miRNA expression in 41 @entity1 (the discovery set) which were dichotomized into; 'high risk'- experienced biochemical failure within 24 months after radical prostatectomy (n=26) and 'low risk' who did not have biochemical failure for at least 35 months (n=15). The validation set consisted of 72 cases. Total RNA was isolated from FFPE cores. cDNA was prepared for each @entity1 and expression miRNA expression was screened by qRT-PCR -based panel. miRNAs were ranked by non-parametric tests. Linear regression models were built to predict biochemical failure. We used TargetScan for miRNA target prediction. Targets were validated by transient transfection of synthetic miRNA precursors followed by qRT-PCR quantification of the targets. Proliferation was assessed by measuring cell viability. RESULTS: We compared the expression of 754 mature @entity1 miRNAs in @entity1 with 'high' or 'low' risk for biochemical failure. We identified 24 miRNAs that were differentially expressed between the risk groups. We developed three logistic regression models, based on the expression of 2-3 miRNAs ( @entity2286 =100% and NPV ranges 86.4-100%). We confirmed the differential expression on the study set and on a larger, independent set of PCa pateints. We also validated one model on an independent set of @entity1 . Further, we show that transfection of @entity20479 and miR-331-3p, featured in the logistic regression models, altered proliferation of @entity21416 and DU145 cells. Target prediction indicated @entity7514 and @entity1722 as potential direct targets and their mRNA expression significantly reduced when @entity20479 and miR-331-3p were overexpressed. CONCLUSIONS: Altered miR-331-3p and @entity20479 expression represent a potential tool for assessing the risk of early biochemical failure. These miRNAs may act through the @entity470 family to induce an alternative way of AR activation.

Use of microRNA signature to distinguish early from late biochemical failure in XXXX .

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity21416 :: ('50652', 'Gene') :: ['PCa3'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer'] @entity7514 :: ('2065', 'Gene') :: ['Erbb3'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressiveness'] @entity470 :: ('1956', 'Gene') :: ['Erbb'] @entity2286 :: ('12211', 'Species') :: ['PPV'] @entity20479 :: ('406943', 'Gene') :: ['miR-152'] @entity1722 :: ('2064', 'Gene') :: ['Erbb2']
@entity263 :: (MESH:D011471,Disease) :: ['prostate cancer']
