Circulating Tumor Cells as Diagnostic and Therapeutic Biomarkers in Hepatocellular Carcinoma: Advancing Precision Oncology Through Liquid Biopsy

Circulating tumor cells (CTCs) are emerging as promising biomarkers in hepatocellular carcinoma (HCC), offering noninvasive insight into tumor biology, progression, and treatment response. Advances in enrichment and single-cell technologies have enabled the characterization of CTCs at genomic, transcriptomic, epigenetic, and proteomic levels. CTC detection correlates with tumor stage, vascular invasion, and alpha-fetoprotein levels, supporting their role in early diagnosis and staging. Specific surface markers such as epithelial cell adhesion molecule, GPC3, ASGPR, and stem cell-associated antigens like CD90 and CD133 help classify CTC subtypes with prognostic and therapeutic relevance. Mesenchymal and hybrid phenotypes, identified via epithelial-to-mesenchymal transition markers, are linked to recurrence and metastasis. Furthermore, CTCs provide a platform for companion diagnostics by reflecting mutational and resistance profiles, particularly in the context of targeted therapies and immune checkpoint inhibitors. Despite current limitations in standardization, sensitivity, and scalability, the integration of CTC analysis into clinical practice holds potential to enhance precision medicine strategies in HCC.