Exosomal proteins as potential markers of tumor diagnosis

Abstract

Liquid biopsy especially that of exosomes carries tumor-specific molecules and provides useful information during tumor development and progression in "real time." Exosomes are membrane-encapsulated vesicles, constantly released by multiple cells, including cancer cells, in large quantities, and are widely present in body fluids. Tumor exosomes can remodel a tumor-supportive microenvironment via cross-talk with target cells. Recent research has mainly focused on exosomal miRNAs and to a small degree on proteins. However, detecting the genome output (active proteins such as phosphoproteins) can provide more direct information about disease progression, such as in the early discovery and monitoring of cancers. This review highlights the unique features of exosomal proteins over traditional serological markers and summarizes their recent use in cancer diagnosis and prognosis. Furthermore, we describe the general protocols of research on exosome proteomics with an emphasis on their clinical use.

Keywords: Cancer biomarker; Detection; Exosomal proteins; Exosomes; Isolation.

Fig. 1

Schematic representation of exosome biogenesis, release, and isolation from the blood. Endocytosis at the plasma membrane forms the early endosome. The inward budding of the membrane of late endosomes and subsequent pinching off of the membrane creates the exosomes, called multivesicular bodies (MVBs). Upon the fusion of MVBs with the plasma membrane, exosomes are released into the extracellular milieu, which enriched in nucleic acid and proteins. Exosomes, cell-free nucleic acid (cfNA), circulating tumor cell can be found and extracted from a blood sample. Improvement in mass spectrometry-based proteomic tools and microfluidic approaches, which coupled with improved purification schemes for exosomes, has allowed more in-depth proteome analyses. The potential of exosomal protein profiles for use as diagnostic biomarkers of disease through a non-invasive blood test