<i>N-</i> glycosylation alterations in expressed prostatic secretions: exploring liquid biopsy biomarkers for prostate cancer diagnosis and disease progression

Prostate cancer (PCa) is among the most common malignancies in men. Liquid biopsies enable repeated sampling of tumor-derived material, including extracellular vesicles (EVs) that provide stable, multianalyte molecular readouts. Expressed prostatic secretion (EPS), obtained directly or as EPS-urine after prostate massage, is an organ-proximal matrix enriched in prostate-derived proteins, metabolites, and prostasome-like EVs, but its use is limited by low volumes, urine dilution, and lack of standardized protocols. Glycosylation, is a non-templated post-translational modification regulated by enzyme networks and nucleotide-sugar availability, allowing glycomic phenotypes to capture disease states beyond gene or protein levels. This review covers studies from 1985 to 2025 on EPS-associated glycosylation in PCa and, despite limited and heterogenous data, consistently reports altered core fucosylation, terminal sialylation, and N- glycan branching. EV-associated glycomes and prostate-specific antigen glycoforms may diverge from bulk EPS glycans, reflecting selective vesicular cargo loading and compartment-specific regulation. Integrating EPS-based glycan profiling with existing tools could enhance PCa diagnosis and longitudinal monitoring. This review synthesizes emerging findings on EPS-derived glycomic alterations in PCa and presents EPS as a promising yet underutilized biofluid for non-invasive biomarker discovery. Nevertheless, rigorous validation through large-scale studies is essential to establish EPS-based glycan biomarkers as reliable diagnostic and prognostic tools for PCa.