Prostate cancer (PCa) is the most commonly diagnosed cancer in males. Early PCa usually shows no clinical symptoms and its primary diagnosis is currently guided by liquid-biopsy testing of serum prostate-specific antigen (PSA). This testing suffers from high false-positive and false-negative rates. Identifying new biomarkers for precise liquid-biopsy detection of PCa is, thus, an acute clinical request. Here, by using an advanced dual-functional aptamer assay, we quantified the extent of glycosylation of PSA circulating in cancer patients' serum, linked it to cancer-related breakage of PSA complexes with serum-circulating proteins, and proved its facility for stratification of primary and metastatic PCa. PSA's "Glycan Score" 100% accurately informed about PCa status in a 30-patient cohort, while serum PSA's concentration correctly classified only 53% of PCa patients and did not inform about their PCa status. The Glycan Score liquid-biopsy test thus has a huge potential for accurate diagnosis and staging of PCa, enabling mass-screening program progress and advanced PCa treatment monitoring.
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