Extracellular vesicles and their nucleic acids for biomarker discovery

Extracellular vesicles (EVs) are a heterogenous population of vesicles originate from cells. EVs are found in different biofluids and carry different macromolecules, including proteins, lipids, and nucleic acids, providing a snap shot of the parental cells at the time of release. EVs have the ability to transfer molecular cargoes to other cells and can initiate different physiological and pathological processes. Mounting lines of evidence demonstrated that EVs' cargo and machinery is affected in disease states, positioning EVs as potential sources for the discovery of novel biomarkers. In this review, we demonstrate a conceptual overview of the EV field with particular focus on their nucleic acid cargoes. Current knowledge of EV subtypes, nucleic acid cargo and pathophysiological roles are outlined, with emphasis placed on advantages against competing analytes. We review the utility of EVs and their nucleic acid cargoes as biomarkers and critically assess the newly available advances in the field of EV biomarkers and high throughput technologies. Challenges to achieving the diagnostic potential of EVs, including sample handling, EV isolation, methodological considerations, and bioassay reproducibility are discussed. Future implementation of ‘omics-based technologies and integration of systems biology approaches for the development of EV-based biomarkers and personalized medicine are also considered

Analysis of AR-FL and AR-V1 in Whole Blood of Patients with Castration Resistant Prostate Cancer as a Tool for Predicting Response to Abiraterone Acetate

PURPOSE: Reliable molecular diagnostic tools are still unavailable for making informed treatment decisions and monitoring the response in patients with castration resistant prostate cancer. We evaluated the significance of whole blood circulating androgen receptor transcripts of full length (AR-FL) and splice variants (AR-V1, AR-V3 and AR-V7) as biomarkers of abiraterone acetate treatment resistance in patients with castration resistant prostate cancer. MATERIALS AND METHODS: After retrospective analysis in 112 prostate specimens AR-FL, AR-V1, AR-V3 and AR-V7 were evaluated in 185 serial blood samples, prospectively collected from 102 patients with castration resistant prostate cancer before and during abiraterone acetate therapy via reverse transcription quantitative polymerase chain reaction. RESULTS: AR-FL was present in all samples while AR-V1, AR-V3, AR-V7 and at least 1 of them was detected in 17%, 55%, 65% and 81% of castration resistant prostate cancer blood samples, respectively. The highest amount of AR-V1 was found in blood of patients whose response time was short and medium in comparison to extended. Patients with a higher level of AR-FL and/or AR-V1 had the shortest progression-free survival and overall survival (p <0.0001). CONCLUSIONS: Blood circulating AR-FL or AR-V1 can serve as blood based biomarkers for identification of the primary resistance to abiraterone acetate and the tool to monitor de novo resistance development during abiraterone acetate treatment