Departments of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Background: Clinically, it is still challenging to differentiate aggressive from non-aggressive prostate cancers (Pca) by non-invasive approaches. Our recent studies showed that overexpression of alpha (1-6) fucosyltransferase played an important role in Pca cells. In this study, we have investigated levels of glycoproteins and their fucosylated glycoforms in sera of Pca patients, as well as the potential utility of fucosylated glycoproteins in the identification of aggressive Pca.
Material and Methods: Serum samples from histomorphology-proven Pca cases were included. Prostate-specific antigen (PSA), tissue inhibitor of metallopeptidase 1 (TIMP1) and tissue plasminogen activator (tPA), and their fucosylated glycoforms were captured by Aleuria Aurantia Lectin (AAL), followed by the multiplex magnetic bead-based immunoassay. The level of fucosylated glycoproteins was correlated with patients' Gleason score of the tumor.
Result: Among three fucosylated glycoproteins, the fucosylated PSA was significantly increased and correlated with the tumor Gleason score (p<0.05). The ratio of fucosylated PSA showed a marked increase in aggressive tumors in comparison to non-aggressive tumors. ROC analysis also showed an improved predictive power of fucosylated PSA in the identification of aggressive Pca.
Conclusions: Our data demonstrated that fucosylated PSA has a better predictive power to differentiate aggressive tumors from non-aggressive tumors, than that of native PSA and two other glycoproteins. The fucosylated PSA has the potential to be used as a surrogate biomarker.
Keywords: prostate cancer, multiplex immunoassay, fucosylated glycoprotein, prostate-specific antigen, TIMP1.