MicroRNAs (miRNAs) are a class of short, single-stranded, noncoding RNAs, with a length of about 18–22 nucleotides. Extracellular vesicles (EVs) are derived from cells and play a vital role in the development of diseases and can be used as biomarkers for liquid biopsy, as they are the carriers of miRNA. Existing studies have found that most of the functions of miRNA are mainly realized through intercellular transmission of EVs, which can protect and sort miRNAs. Meanwhile, detection sensitivity and specificity of EV-derived miRNA are higher than those of conventional serum biomarkers. In recent years, EVs have been expected to become a new marker for liquid biopsy. This review summarizes recent progress in several aspects of EVs, including sorting mechanisms, diagnostic value, and technology for isolation of EVs and detection of EV-derived miRNAs. In addition, the study reviews challenges and future research avenues in the field of EVs, providing a basis for the application of EV-derived miRNAs as a disease marker to be used in clinical diagnosis and even for the development of point-of-care testing (POCT) platforms.

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Background: Exosomes have great potential as new biomarkers in liquid biopsy. However, due to the limitations of exosome extraction and component analysis procedures, further clinical applications of exosomes are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies. Results: In this study, CEA+ exosomes were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA+ exosomes was determined. It was found that the NPr of CEA+ exosomes in tumor group was higher than that of healthy group. We further analyzed the exosome-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA+ exosomes was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer. Conclusions: This study demonstrates that the dsDPr of CEA+ exosomes can effectively distinguish exosomes derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis.

Background Small extracellular vesicles (sEVs) have great potential as new biomarkers in liquid biopsy. However, due to the limitations of sEVs extraction and component analysis procedures, further clinical applications of sEVs are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies. Results In this study, CEA+ sEVs were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA+ sEVs was determined. It was found that the NPr of CEA+ sEVs in tumor group was higher than that of healthy group. We further analyzed the sEV-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA+ sEVs was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer. Conclusions This study demonstrates that the dsDPr of CEA+ sEVs can effectively distinguish sEVs derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis.