Aberrantly glycosylated PSMA in urine as a potential marker for prostate cancer

Early detection of prostate cancer (PCa) requires the development of reliable non-invasive biomarkers. In this study, we describe a simple, non-invasive assay to detect a prostate-specific membrane antigen (PSMA) glycoisoform directly from unprocessed urine. PSMA was analyzed in urine samples from PCa patients ( n = 40) and benign controls ( n = 37) using lectin MGL-coated europium-doped nanoparticles. MGL showed enhanced binding to PCa-derived PSMA, indicating aberrant glycosylation. Evaluation of individual samples demonstrated that the PSMA-MGL glycovariant assay significantly discriminated PCa from benign conditions ( p = 0.01 pilot, p = 0.02 validation). Moreover, this assay exhibited a three-fold improvement in sensitivity over conventional antibody-based PSMA detection. ROC analysis showed an AUC of 0.648 for PSMA-MGL, which increased to 0.734 when combined with free-PSA and urinary creatinine, highlighting the enhanced diagnostic potential of this multimarker, non-invasive approach. • This study highlights the importance of glycosylated PSMA in early detection of prostate cancer. • The study introduces a glycovariant assay to detect altered glycosylation of prostate-specific membrane antigen (PSMA) in patient samples. • Shows that urinary PSMA levels are significantly elevated in the prostate cancer patients compared to benign controls ( p = 0.02) • Demonstrates that the glycovariant assay is 3-times more sensitive than the conventional immunoassay. • This study highlights the potential of using novel urinary biomarkers in combination with the already existing ones to improve prostate cancer diagnostics.