Glycoproteomics of body fluids and derived exosomes in hepatocellular carcinoma

Hepatocellular carcinoma (HCC), a prevalent malignant tumor, is characterized by occult early symptoms, leading to most patients being diagnosed at advanced stages. This diagnostic delay significantly contributes to the high mortality and limited therapeutic efficacy observed in HCC. Therefore, the development and application of accurate early detection methods and efficacious treatment strategies are essential for improving patient survival and overall clinical outcomes. Glycoproteomics focuses on the characterization of glycosylation sites and site-specific glycans. As one of the most prevalent post-translational modifications of proteins, aberrant glycosylation plays a critical role in the initiation, progression, diagnosis and treatment of HCC. In-depth investigation of abnormal glycoproteins in HCC holds substantial scientific and clinical significance for unraveling its pathogenesis, identifying effective diagnostic biomarkers, and pinpointing potential therapeutic targets. Body fluids and the derived exosomes have emerged as a pivotal research frontier, owing to their distinctive advantages: non-invasiveness, a wealth of disease-associated information, and ease of collection. Based on this, this review elaborates on the research strategies of HCC glycoproteomics and provides a detailed description of the analysis of body fluids and derived exosomes, to explore potential biomarkers in the pathogenesis of HCC, thereby providing strong support for the early detection and personalized treatment.