This urine exosome gene expression assay is a noninvasive, urinary 3-gene expression assay that discriminates high-grade (≥GS7) from low-grade (GS6) cancer and benign disease. In this study, the urine exosome gene expression assay was associated with improved identification of patients with higher-grade prostate cancer among men with elevated PSA levels and could reduce the total number of unnecessary biopsies.

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A novel molecular signature (EXO106 score) derived from non-DRE urine demonstrated independent, negative predictive value for the diagnosis of high-grade PCa from initial biopsy for men with 'gray zone' serum PSA levels. Its use in the biopsy decision process could result in fewer prostate biopsies for clinically insignificant disease.

When analyzed from transformed cell lysates, pp60v-src, the product of the Rous sarcoma virus src gene, typically appears as a single polypeptide of 60,000 molecular weight, phosphorylated at two major sites, an amino-terminal region serine residue and carboxy-terminal region tyrosine residue. We describe here the identification of variant forms of pp6-vsrc present in transformed cell lysates that exhibited an altered electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels. This change in migration appeared to be the result of some alteration in the amino-terminal portion of the molecule and paralleled the appearance of extensive amino-terminal region tyrosine phosphorylation on the pp60v-src molecule. These structural modifications were further correlated with a dramatic increase in the protein kinase-specific activity of pp6Ovsrc. The detection of these variant forms of pp60v"src depended on the prior treatment of the transformed cell cultures with vanadium ions or the inclusion in the cell disruption buffer of Mg2+ or ATP-Mg2+. The implication is that modified, highly active forms of the pp60ovsrc protein exist in transformed cells, but are transient and rapidly converted to stable forms, possibly by specific dephosphorylation. We suggest that amino-terminal region tyrosine phosphorylation of pp60vsrc, presumably the result of autophosphorylation, serves to greatly enhance src protein enzymatic activity, but that much of the regulation of this transforming protein's function may involve a phosphotyrosyl protein phosphatase.The protein responsible for the oncogenic capabilities of Rous sarcoma virus (RSV) is pp6Ov-sr, a phosphoprotein encoded by the viral src gene (2,20,35,46). pp6,v-src appears to possess at least one enzymatic activity, that of a tyrosine-specific protein kinase (6,12,13,18,21,28,29,31,41). pp6Ov-src as isolated from transformed cell lysates itself contains two major phosphorylated residues: a phosphoserine located near the amino-terminal end of the protein (ser-17), which appears to be the result of phosphorylation by a cellular cyclic AMP-dependent protein kinase (7,8), and a phosphotyrosine residue, initially mapped to the carboxyterminal one-third of the polypeptide (7,8) and subsequently identified as the tyrosine residue at amino acid position 416 in the pp60v-src molecule (33, 42). Phosphorylation of tyrosine 416 may be the result of pp6Ov-src autophosphorylation since this same tyrosine residue was also found to be phosphorylated in vitro by purified pp60-src enzyme preparations (9,34,42 ed with these mutants were morphologically transformed and possessed pp6O-src tyrosine kinase activities similar to wild-type levels. These two studies therefore seem to indicate that phosphorylation of pp60-src, at either tyr416 or ser-17, plays little, if any, role in the function of src.We too have been interested in evaluating the functional consequences of phosphorylation, specifically tyrosine phosphorylation, on the pp6ov-sr, protein. However, our approach to this problem differ...

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