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Review
. 2019 Apr 6;9(2):20180077.
doi: 10.1098/rsfs.2018.0077. Epub 2019 Feb 15.

Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer

Affiliations
Review

Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer

Jan Tkac et al. Interface Focus. .

Abstract

The initial part of this review details the controversy behind the use of a serological level of prostate-specific antigen (PSA) for the diagnostics of prostate cancer (PCa). Novel biomarkers are in demand for PCa diagnostics, outperforming traditional PSA tests. The review provides a detailed and comprehensive summary that PSA glycoprofiling can effectively solve this problem, thereby considerably reducing the number of unnecessary biopsies. In addition, PSA glycoprofiling can serve as a prognostic PCa biomarker to identify PCa patients with an aggressive form of PCa, avoiding unnecessary further treatments which are significantly life altering (incontinence or impotence).

Keywords: biomarkers; diagnostics; glycans; lectins; prostate cancer; prostate-specific antigen.

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Conflict of interest statement

We declare we have no competing interests.

Figures

Figure 1.
Figure 1.
Black box (left) image: natural PSA (KLK3, hk3; PDB code 3QUM) exhibiting a complex tri-antennary glycan at Asn61, with terminal sialic acid units, often N-acetyl neuraminic acid (Neu5Ac) (magenta). The active site is in an open state permitting access of substrates, e.g. shown as a stick model bound to the protein. At the opposite side to the active site, an O-glycan is linked to Thr125, which consists of GalNAc-Gal (insert). The figure is taken from an open access publication [17]. Green box (middle) image: typical glycan structures present at Asn61 on PSA from healthy men or men with BPH. Red box (right) image: typical glycan structures present at Asn61 of PSA from PCa patients. Glycans present at position Asn61 were compiled from various sources [,–22]. A typical glycan structure present at Asn102 on PSA as a result of an unusual missense mutation (the rs61752561 in KLK3 genes) resulting in the conversion of Asp102 to Asn102 is positioned between the green and red boxes. (Online version in colour.)
Figure 2.
Figure 2.
In the process of tumour cell dissociation/invasion, glycans interfere with cell–cell adhesion via electrostatic repulsion mediated by negatively charged sialic acids and by branched N-glycans present on E-cadherin (upper left). Expression of gangliosides in the cancer cell membrane can also modulate signal transduction, activating various cellular pathways that induce tumour growth and progression (upper right). In the process of tumour cell migration, integrins show altered glycosylation in both O-linked and N-linked glycans. Terminal sialylation interferes with cell-extracellular matrix (ECM) interactions, promoting an increased migratory and invasive phenotype (lower left). The aberrant glycosylation of vascular endothelial growth factor receptor (VEGFR) modulates its interaction with galectins and is associated with tumour angiogenesis. The tumour-associated carbohydrate determinants sialyl Lewis x (SLex) and SLea serve as ligands for the adhesion receptors expressed in activated endothelial cells (E-selectin), promoting cancer cell adhesion/metastasis. Reprinted with permission from Pinho & Reis [33] (copyright © 2015 Nature). (Online version in colour.)

References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. 2015. Global cancer statistics, 2012. CA: Cancer J. Clin. 65, 87–108. ( 10.3322/caac.21262) - DOI - PubMed
    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, E359–E386. ( 10.1002/ijc.29210) - DOI - PubMed
    1. O'Reilly J-A, O'Kennedy RJ. 2017. Prostate cancer detection: complexities and strategies. J. Cancer Treat. Diagn. 2, 18–25.
    1. Rodríguez JZ, O'Kennedy R. 2017. New approaches for the development of diagnostic systems for prostate cancer. Asian Hosp. Healthc. Manag. 36, 18–23.
    1. Ablin RJ, Piana R. 2014. The great prostate hoax: how big medicine hijacked the PSA test and caused a public health disaster. New York, NY: Palgrave McMillian.