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Aberrant PSA glycosylation—a sweet predictor of prostate cancer

Abstract

Prostate cancer—the most commonly diagnosed cancer in men worldwide—can have a substantial effect on quality of life, regardless of the route the cancer takes. The serum PSA assay is the current gold standard option for diagnosing prostate cancer. However, a growing body of evidence suggests that PSA screening for prostate cancer results in extensive overdiagnosis and overtreatment. It is increasingly evident that the potential harm from overdiagnosis (in terms of unnecessary biopsies) must be weighed against the benefit derived from the early detection and treatment of potentially fatal prostate cancers. Rapid screening methods have been used to analyse glycosylation patterns on glycoproteins in large cohorts of patients, enabling the identification of a new generation of disease biomarkers. Changes to the expression status of certain glycan structures are now widely thought to be common features of tumour progression. In light of this development, much research has focused on the potential role of altered PSA glycosylation patterns in discriminating between significant and insignificant prostate cancers, with the aim of developing a more reliable diagnostic tool than the current serum PSA test.

Key Points

  • Serum PSA testing is the current gold standard option for screening and diagnosing prostate cancer

  • Expert opinions regarding PSA testing are divided; the benefits of early diagnosis must be weighed against the harm caused by overdiagnosis

  • PSA isoforms represent potential biomarkers for monitoring disease

  • Aberrant glycosylation patterns occur when changes to cellular pathways affect glycan processing; these patterns are a common feature of many diseases

  • Glycan profiling has shown potential as a novel tool for distinguishing clinically significant prostate cancer from clinically insignificant prostate cancer

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Figure 1: PSA biosynthesis.
Figure 2: The complete amino acid composition of PSA with highlighted cleavage points.
Figure 3: Symbolic diagrams to depict N-linked monosaccharides and linkages of the three general N-linked glycan structures (as devised by Harvey and co-workers98).
Figure 4: Methodology for glycan release, fluorescent labelling, normal-phase high-performance liquid chromatography (HPLC) profiling, structure assignment, and quantitation.

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Acknowledgements

P. J. Conroy and R. J. O'Kennedy are supported by the Science foundation, Ireland, under CSET grant number 10/CE/B1821. All authors are funded by the Irish Cancer Society Programme grant PCI11WAT as part of the Prostate Cancer Research Consortium, Dublin, Ireland.

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S. Gilgunn, P. J. Conroy, and R. J. O'Kennedy devised the concept of the manuscript. S. Gilgunn carried out the research. S. Gilgunn, P. J. Conroy, and R. J. O'Kennedy wrote the manuscript. R. J. O'Kennedy, R. Saldova, and P. M. Rudd reviewed and edited the manuscript prior to submission.

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Correspondence to Richard J. O'Kennedy.

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Gilgunn, S., Conroy, P., Saldova, R. et al. Aberrant PSA glycosylation—a sweet predictor of prostate cancer. Nat Rev Urol 10, 99–107 (2013). https://doi.org/10.1038/nrurol.2012.258

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