Diagnostic and prognostic significance of circulating extracellular vesicles in gastrointestinal cancers

Gastrointestinal (GI) cancers represent a significant global health burden, accounting for over one-third of cancer-related deaths globally. Regardless of advancements in treatment procedures, the high mortality rate underscores the crucial need for novel diagnostic biomarkers and therapeutic strategies. Extracellular vesicles (EVs) appeared as fundamental facilitators of intercellular interaction, influencing gene expression as well as cellular function through the transfer of nucleic acids, proteins, and lipids. EVs play dual roles in maintaining intestinal homeostasis under physiological conditions and driving tumorigenesis in pathological states. In GI cancers, EVs contribute to tumor progression by modulating the tumor microenvironment (TME), promoting angiogenesis, epithelial-to-mesenchymal transition (EMT), immune evasion, and metastasis. Moreover, EVs portray a vital role in creating pre-metastatic site, reprogramming immune cells, and facilitating therapeutic resistance through the transfer of resistance-associated molecules. The clinical potential of EVs extends to their utility as liquid biopsy biomarkers, offering a non-invasive approach for early diagnosis, prognostication, and treatment monitoring. EV-miRNAs and EV-long non-coding RNAs demonstrate significant diagnostic and prognostic value in GI cancers. This review provides a widespread impression of the biogenesis, molecular properties, and functional roles of EVs in GI cancers, with a focus on their clinical utility.