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

Table 2 Composition of exosome

Biomolecule	Function	Ref.
Hsc70, Hsp70, Hsp60, Hsp90 (HSPs)	Mediate protein distribution in ILVs (exosome precursors) and the inclusion of cytoskeleton proteins	[21,22,31]
GTPase Rab, flotillins, annexins, ARF6	Participate in exosome release and membrane fusion	[32,33]
Major histocompatibility complex class II molecules	Function not detailed in this text, likely related to immune response	[34]
Programmed cell death 6-interacting proteins	Play a role in programmed cell death	[35]
Tsg101 proteins	Are involved in the sorting and transportation of exosomes	[22]
CD9, CD63, CD81 (tetraspanin family transmembrane proteins)	Function not fully described, likely related to exosome structure and function	[35]
Transforming growth factor-β, apoptosis - related factor ligands (in tumor cell secreted exosomes)	Associated with tumor - specific processes	[36]
Dipeptidyl peptidase IV, matrix metallopeptidase 9	Participate in extracellular matrix remodeling, related to tumor invasion and metastasis	[37]
Epithelial cell adhesion molecule, epidermal growth factor receptor, survivin, insulin-like growth factor 1 receptor	Can be used as biomarkers for clinical diagnosis and prognosis	[38]
miRNA	Intercellular transport via exosomes may critically regulate gene expression and protein translation	[36,39-44]
	Short sequence motifs (EXOmotifs) guide miRNA into exosomes
	hnRNPA2B1 selectively binds miRNA, recognizing EXOmotifs and controlling its encapsulation within exosomes
	RNA binding proteins and RNA sequence motifs contribute to its selective sorting into exosomes
	Encapsulated in exosomes, RNA binding proteins protect miRNA from hydrolytic degradation, enabling it to exercise effects through cell-to-cell communication
circRNA	Part of the diverse ncRNA species in exosomes; specific functions not elaborated in the given text	[39,40]
lncRNA	Part of the diverse ncRNA species in exosomes; specific functions not elaborated in the given text	[39,40]
EXOmotifs	Guide miRNA into exosomes	[42]
hnRNPA2B1	Selectively binds exosomal miRNAs, recognizes EXOmotifs, and controls their encapsulation within exosomes	[42]
RNA binding proteins	Contribute to the selective sorting of miRNA into exosomes and protect RNAs (including miRNA) from hydrolytic degradation when encapsulated in exosomes	[36,43]
Cholesterol	Involved in exosome formation and release; contributes to the overall lipid composition affecting exosome properties, though its concentration may differ from parent cells	[32,45-47]
Sphingolipids (incl. Sphingomyelin)	Involved in exosome formation and release; sphingomyelin has a higher concentration in exosomes compared to parent cells	[32,45-47]
Phosphatidylcholine	Participates in exosome formation and release; present at a reduced content in exosomes relative to parent cells	[32,45-47]
Phosphatidylethanolamine	Involved in exosome formation and release; shows an observable enrichment in exosomes	[32,45-47]
Ceramide	Plays a role in exosome formation and release	[32,45,46]
Glycerophospholipids	Contribute to exosome formation and release	[32,45,46]
Lipid rafts	Implicated in exosome formation and help facilitate the secretion of specific molecules into the extracellular space; contribute to exosome’s permeability and circulating stability, making exosomes suitable for drug delivery	[45,48,27]

HSPs: Heat shock proteins; ILV: Intraluminal vesicle; miRNA: MicroRNA; lncRNA: Long noncoding RNA; circRNA: Circular RNA; Tsg101: Tumor susceptibility gene 101; ARF6: ADP ribosylation factor 6; hnRNPA2B1: Heterogeneous nuclear ribonucleoprotein A2B1.