The glycoprofiling of two
proteins, the free form of the
prostate-specific antigen (fPSA) and zinc-α-2-glycoprotein (ZA2G), was assessed to determine their suitability as
prostate cancer (PCa)
biomarkers. The glycoprofiling of
proteins was performed by analysing changes in the
glycan composition on fPSA and ZA2G using
lectins (
proteins that recognise
glycans, i.e. complex
carbohydrates). The specific glycoprofiling of the
proteins was performed using magnetic beads (MBs) modified with
horseradish peroxidase (HRP) and
antibodies that selectively enriched fPSA or ZA2G from human serum samples. Subsequently, the antibody-captured
glycoproteins were incubated on
lectin-coated ELISA plates. In addition, a novel
glycoprotein standard (GPS) was used to normalise the assay. The glycoprofiling of fPSA and ZA2G was performed in human serum samples obtained from men undergoing a prostate biopsy after an elevated serum PSA, and
prostate cancer patients with or without prior
therapy. The results are presented in the form of an ROC (Receiver Operating Curve). A DCA (Decision Curve Analysis) to evaluate the clinical performance and net benefit of fPSA
glycan-based
biomarkers was also performed. While the glycoprofiling of ZA2G showed little promise as a potential PCa
biomarker, the glycoprofiling of fPSA would appear to have significant clinical potential. Hence, the GIA (Glycobiopsy ImmunoAssay) test integrates the glycoprofiling of fPSA (i.e. two
glycan forms of fPSA). The GIA test could be used for early diagnoses of PCa (AUC = 0.83; n = 559 samples) with a potential for use in
therapy-monitoring (AUC = 0.90; n = 176 samples). Moreover, the analysis of a subset of serum samples (n = 215) revealed that the GIA test (AUC = 0.81) outperformed the PHI (Prostate Health Index) test (AUC = 0.69) in discriminating between men with
prostate cancer and those with benign serum PSA elevation.