Secretory vesicle analysis for discovery of low abundance plasma biomarkers.

ABSTRACT

BACKGROUND: Pathological conditions can be reflected, as well as propagated, by changes in the expression patterns of secreted proteins. Protein secretion may occur by signal sequence dependent or independent mechanisms and many secreted proteins with desirable biomarker characteristics appear to be low abundance proteins in body fluids. Both factors complicate disease-associated secreted protein discovery. OBJECTIVE: To enhance the discovery of low abundance, physiologically relevant, plasma protein biomarkers. METHODS: Biomarker discovery has been performed in media, body fluids or tissue homogenates. A comparative analysis of the contents of secretory vesicles isolated directly from affected tissues or model systems substantially improves the detection of relevant, low abundance plasma biomarkers. RESULTS: Evidence supporting this approach is provided from pilot experiments in prostate cancer.