Application of exosomes as liquid biopsy in clinical diagnosis

Abstract

Liquid biopsy refers to the sampling and molecular analysis of the biofluids of circulating tumor cells, extracellular vesicles, nucleic acids, and so forth. Exosomes are small extracellular vesicles with sizes between 30-150 nm. They are secreted by multivesicular bodies through exocytosis in live cells and can participate in intercellular communication due to their contents, including nucleic acids, proteins, and lipids. Herein, we investigate publication frequencies on exosomes over the past 10 years, and review recent clinical studies on liquid biopsy of exosomes in the fields of oncology, pregnancy disorders, cardiovascular diseases, and organ transplantation. We also describe the advantages of exosomes as an effective liquid biopsy tool and the progression of exosome extraction methods. Finally, we depict the commercial development of exosome research and discuss the future role of exosomes in liquid biopsy.

Fig. 1

Publication frequencies of studies investigating different contents of exosomes as liquid biopsy for disease diagnosis over the past 10 years based on the PubMed search, January 2020

Fig. 2

Biogenesis, secretion, composition, and application of exosomes as liquid biopsy. Exosomes, originating from the endosomal pathway via the formation of late endosomes or multivesicular bodies, enclose a variable spectrum of molecules characterized by parent cells, including nucleic acids (DNA, mRNA, miRNA, lncRNA, circRNA, etc.), proteins, and lipids, which shows great promise in clinical applications in cancer, pregnancy disorders, cardiovascular diseases and organ transplantation

Fig. 3

Exosomes in liver metastasis of colorectal cancer. Stromal cell-derived exosomes can carry bioactive molecules (e.g., miR-92a-3p) to CRC cells and enhance epithelial-mesenchymal transition and cell stemness to promote liver metastasis. Many other miRNAs (e.g., miR-193a, miR-21, miR-25-3p, miR-18a, miR-17-5p, miR-141-3p, miR-548c-5p, miR-375, and miR-6803-5p) encapsulated in exosomes from primary CRC cells, which flow to the liver via blood circulation and lead to liver metastasis, can be candidates for prognosis