Prospects of CD44 in hepatocellular carcinoma: An emerging biomarker and therapeutic target

CD44, a single-transmembrane glycoprotein with diverse functional roles, has emerged as a critical regulator of tumor behavior, particularly in hepatocellular carcinoma (HCC). Elevated CD44 expression in HCC correlates with aggressive disease progression, positioning it as a promising diagnostic and prognostic biomarker. At the molecular level, CD44 orchestrates key oncogenic processes, including enhanced cellular proliferation, accelerated cell cycle progression, and increased migratory capacity, thereby driving HCC pathogenesis. As therapeutic strategies for HCC become more aggressive, invasive interventions are associated with adverse clinical outcomes, highlighting the need for targeted approaches. This review comprehensively analyzes current literature on CD44, addressing its structural diversity, isoform-specific functions, and signaling mechanisms in HCC. Furthermore, we discuss its prognostic significance, role in therapeutic resistance, and potential as a molecular target. By synthesizing these findings, this work aims to provide novel insights into early detection, accurate diagnosis, and the development of precision therapies for HCC, ultimately improving clinical outcomes.