Exosomal biomarkers: A novel frontier in the diagnosis of gastrointestinal cancers

Table 1 Exosome formation and composition

Aspect	Details	Ref.
Origin	Derived from endosomal structures through endocytosis	[10]
	Invaginated endosomes form from the plasma membrane
Content sorting & packaging	Tightly regulated process of active sorting and packaging of diverse contents	[11,12]
Diverse contents	Lipids, proteins, DNA, mRNA, miRNAs (18-25 nt), lncRNA (> 200 nt), circRNA	[11,13,14]
Protein components	Rab family proteins, sorting - associated proteins, tetraspanins, HSPs, integrins, vacuolar proteins. Co-existence depends on specific proteins and their functions	[15]
ESCRT - dependent biogenesis	ESCRT-0 recognizes ubiquitinated cargo, starting the pathway	[16-19]
	Tsg101 in ESCRT-I forms a complex with ubiquitinated cargo, activating ESCRT-II
	ESCRT-II leads to ESCRT - III formation etc.
	ESCRT-III recruits deubiquitination machinery, packages cargo, promotes vesicle budding. Inward buds mature into MVBs
	ESCRT-III is degraded by an ATPase, regulated by Rab family proteins
Tetraspanins’ role	Transmembrane proteins that induce membrane - curved structures for vesicle formation	[20]
HSPs’ role	Mediate protein distribution in ILVs (exosome precursors) and include cytoskeleton proteins	[21,22]
RNA - related features	Enrichment of miRNAs with 3’-end nucleotide additions and 5’-terminal oligopyrimidine	[23-26]
	Specific RNA modifications during exosome formation enrich specific RNA species
	RNAs can induce genetic and epigenetic modifications in recipient cells
Lipid structure	Cholesterol, phospholipids, glycerophospholipids, sphingolipids, ceramides form a stable bilayer membrane for exosomes	[27]

miRNA: MicroRNA; lncRNA: Long noncoding RNA; circRNA: Circular RNA; HSPs: Heat shock proteins; ESCRT: Endosomal sorting complex required for transport; MVB: Multivesicular body; ILV: Intraluminal vesicle; Tsg101: Tumor susceptibility gene 101.