Abstract

We have developed a novel, versatile, multiplexed exosome-based diagnostic platform that can identify highly specific and sensitive disease biosignatures. This platform has been used to identify a plasma-based exosome biosignature for prostate cancer (PCa) that is superior to current tests, which rely on increased levels of either PSA in the blood or elevated levels of the PCA3 transcript in the urine. Unfortunately, PSA levels can also be elevated due to confounding conditions like benign prostate hyperplasia (BPH) and prostatitis. PCA3, while appearing to be prostate cancer specific, only offers moderate benefit over the performance of PSA, and requires a digital rectal exam to obtain a suitable specimen for analysis. The screening and diagnosis of PCa would be significantly improved by identifying biomarkers that are both highly specific and sensitive as well as easily surveyed from the blood or urine. Exosomes are endosome-derived vesicles between 40-100 nm in diameter that are secreted by many cell types including the epithelial cells of the prostate. In blood exosomes appear to participate in cellular communication by transporting mRNAs, microRNAs and proteins from their cell of origin to target cells where they can elicit biological responses. The quantity and protein topography of exosomes shed from cancer cells varies considerably compared to those shed from normal cells. Thus, the concentration of plasma exosomes with molecular markers indicative of the disease state can be used as a robust and informative blood-based biosignature for PCa and other diseases.