Exosomes in bodily fluids are a highly stable resource of disease biomarkers

Abstract

Biomarkers are measurable indicators of a biological state. As our understanding of diseases meliorates, it is generally accepted that early diagnosis renders the best chance to cure a disease. In the context of proteomics, the discovery phase of identifying bonafide biomarkers and the ensuing validation phase involving large cohort of patient samples are impeded by the complexity of bodily fluid samples. High abundant proteins found in blood plasma make it difficult for the detection of low abundant proteins that may be potential biomarkers. Extracellular vesicles (EVs) have reignited interest in the field of biomarker discovery. EVs contain a tissue-type signature wherein a rich cargo of proteins and RNA are selectively packaged. In addition, as EVs are membranous structures, the luminal contents are protected from degradation by extracellular proteases and are highly stable in storage conditions. Interestingly, an appealing feature of EV-based biomarker analysis is the significant reduction in the sample complexity compared to whole bodily fluids. With these prescribed attributes, which are the rate-limiting factors of traditional biomarker analysis, there is immense potential for the use of EVs for biomarker detection in clinical settings. This review will discuss the current issues with biomarker analysis and the potential use of EVs as reservoirs of disease biomarkers.

Exosome mediated communication within the tumor microenvironment

“…Therefore, considerable focus has shifted to studying and identifying cancerspecific molecular signatures that can be utilized for detection of the disease at an early stage. To this end, much like circulating tumor cells, exosomes carry a wealth of information about the disease characteristics in the form of proteins, lipids, nucleic acids and metabolites that are shed from tumor cells into the exosomes [98]. Besides being secreted by different types of cells in vitro, studies have confirmed the presence of exosomes from various biological fluids including blood, urine, saliva, ascites, cerebrospinal fluid, synovial fluid, breast milk, and bronchoalveolar lavage [99].…”

“…The complexity of the plasma protein content poses a considerable hurdle in this developmental path since the useful biomarkers are often in a very low concentration and are dominated by other abundant proteins [98]. Exosomes on the other hand provide a much cleaner clinical sample devoid of plasma proteins and thus make the analysis and biomarker validation easier.…”

Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells

“…Indeed, EVs are emerging as a unique mechanism for enriching low-level antigens for cancer diagnosis (76), and recent studies using T. cruzi-specific RNA aptamers detected antigens in TESA preparations or serum from mice with acute or chronic T. cruzi infection (77).…”

Phosphoproteins in extracellular vesicles as candidate markers for breast cancer

“…The recent discovery of extracellular vesicles (EVs), including microvesicles and exosomes, and their potentially important cellular functions in tumor biology and metastasis has presented them as intriguing sources for biomarker discovery and disease diagnosis (4)(5)(6). Critical for immune regulation and intercellular communication, EVs have many differentiating characteristics of cancer cell-derived cargo, including mutations, active miRNAs, and signaling molecules with metastatic features (7,8).…”