Hepatocellular Carcinoma and Extracellular Vesicles: From Pathology and Microbial Crosstalk to Therapeutic Strategies

Abstract

Extracellular vesicles are minute membrane bound entities secreted by almost every eukaryotic cell, and they are now recognized as vital mediators of intercellular communication in hepatic malignancies. Their cargo of proteins, lipids, messenger ribonucleic acid, micro ribonucleic acid, long noncoding ribonucleic acid, circular ribonucleic acid, and metabolites mirrors the biological condition of the parent cell. Within the domain of hepatocellular carcinoma these vesicles have been shown to orchestrate a wide spectrum of processes that include cellular proliferation, epithelial to mesenchymal transition, vascular remodeling, stromal recruitment, immune evasion, and therapeutic resistance¹². They also carry enormous potential as diagnostic and prognostic biomarkers because their content can be retrieved from circulating blood and other body fluids with considerable stability³⁴.

This integrative systematic review synthesises mechanistic and translational data from twelve pivotal experimental and clinical studies to delineate the ways by which extracellular vesicles contribute to liver oncogenesis. Evidence is examined from cell line investigations, xenograft models, proteomic and transcriptomic analyses, as well as patient derived cohorts. A central conclusion emerges that vesicle mediated molecular trafficking is not epiphenomenal but rather instrumental to tumour initiation, propagation, and dissemination. Moreover, extracellular vesicles can be engineered as drug delivery vectors or as targets for therapeutic interception, although formidable technical barriers remain. The discussion emphasises the urgent need for standardized isolation protocols, rigorous characterization criteria, and multicentre prospective validation in order to translate these laboratory insights into robust clinical tools