Urinary Extracellular Vesicles as Potential Biomarkers for Urologic Cancers: An Overview of Current Methods and Advances

SIMPLE SUMMARY: The diagnostic and monitoring techniques used for urologic cancers comprise a group of invasive methodologies that still lack sensitivity and specificity. Therefore, the search for a non-invasive alternative is of extreme importance. Urinary extracellular vesicles are an emerging source of biomarkers that have the potential to be used in cancer detection and management, in a minimally invasive way. However, the increasing interest, allied to the absence of standardization and consensus in strategies to isolate and characterize these vesicles, results in a vast list of candidate biomarkers that present no significant overlap. In this review, we show the variability in the methods implemented to obtain these vesicles and focus on microRNA and protein-derived urinary extracellular vesicles as candidate biomarkers for prostate, bladder and kidney cancers. ABSTRACT: Urologic cancers are a heterogeneous group of tumors, some of which have poor prognosis. This is partly due to the unavailability of specific and sensitive diagnostic techniques and monitoring tests, ideally non- or minimally invasive. Hence, liquid biopsies are promising tools that have been gaining significant attention over the last decade. Among the different classes of biomarkers that can be isolated from biofluids, urinary extracellular vesicles (uEVs) are a promising low-invasive source of biomarkers, with the potential to improve cancer diagnosis and disease management. Different techniques have been developed to isolate and characterize the cargo of these vesicles; however, no consensus has been reached, challenging the comparison among studies. This results in a vast number of studies portraying an extensive list of uEV-derived candidate biomarkers for urologic cancers, with the potential to improve clinical outcome; however, without significant validation. Herein, we review the current published research on miRNA and protein-derived uEV for prostate, bladder and kidney cancers, focusing on different uEV isolation methods, and its implications for biomarker studies.