Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Aberrant PSA glycosylation—a sweet predictor of prostate cancer

Nature Reviews Urology volume 10, pages 99–107 (2013)Cite this article

Subjects

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

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Ferlay, J., Parkin, D. M. & Steliarova-Foucher, E. Estimates of cancer incidence and mortality in Europe in 2008. Eur. J. Cancer 46, 765–781 (2010).

    Article  CAS  PubMed  Google Scholar 

  2. Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2012. CA Cancer J. Clin. 62, 10–29 (2012).

    Article  PubMed  Google Scholar 

  3. Lilja, H., Ulmert, D. & Vickers, A. J. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat. Rev. Cancer 8, 268–278 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. Ward, M., Catto, J. W. & Handy, F. Prostate specific antigen: biology, biochemistry and available commercial assays. Ann. Clin. Biochem. 38, 633–651 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Kufe, D. W. et al. (Eds) in Holland-Frei Cancer Medicine 6th edn (B. C. Decker, Hamilton, ON, USA, 2003).

    Google Scholar 

  6. Kirk, D. MRC study: when to commence treatment in advanced prostate cancer. Prostate Cancer Prostatic Dis. 1, 11–15 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Hoffman, R. M. Clinical practice. Screening for prostate cancer. N. Engl. J. Med. 365, 2013–2019 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Bott, S. R. J. Prostate cancer management: 2. An update on locally advanced and metastatic disease. Postgrad. Med. J. 79, 643–645 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Heidenreich, A. et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur. Urol. 59, 61–71 (2011).

    Article  PubMed  Google Scholar 

  10. Lilja, H., Oldbring, J., Rannevik, G. & Laurell, C. B. Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen. J. Clin. Invest. 80, 281–285 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pinsky, P. F. et al. Prostate volume and prostate-specific antigen levels in men enrolled in a large screening trial. Urology 68, 352–356 (2006).

    Article  PubMed  Google Scholar 

  12. Thompson, I. M. et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA 294, 66–70 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Gleason, D. F. & Mellinger, G. T. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J. Urol. 111, 58–64 (1974).

    Article  CAS  PubMed  Google Scholar 

  14. Johnstone, P. A. S., Rossi, P. J., Jani, A. B. & Master, V. “Insignificant” prostate cancer on biopsy: pathologic results from subsequent radical prostatectomy. Prostate Cancer Prostatic Dis. 10, 237–241 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Mikolajczyk, S. D., Song, Y., Wong, J. R., Matson, R. S. & Rittenhouse, H. G. Are multiple markers the future of prostate cancer diagnostics? Clin. Biochem. 37, 519–528 (2004).

    Article  CAS  PubMed  Google Scholar 

  16. Young, C. Y., Andrews, P. E., Montgomery, B. T. & Tindall, D. J. Tissue-specific and hormonal regulation of human prostate-specific glandular kallikrein. Biochemistry 31, 818–824 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Yousef, G. M., Luo, L. Y. & Diamandis, E. P. Identification of novel human kallikrein-like genes on chromosome 19q13.3-q13.4. Anticancer Res. 19, 2843–2852 (1999).

    CAS  PubMed  Google Scholar 

  18. Nelson, P. S. et al. Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. Proc. Natl Acad. Sci. USA 96, 3114–3119 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yousef, G. M. & Diamandis, E. P. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr. Rev. 22, 184–204 (2001).

    CAS  PubMed  Google Scholar 

  20. Lilja, H. A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J. Clin. Invest. 76, 1899–1903 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lilja, H. et al. Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. Clin. Chem. 37, 1618–1625 (1991).

    CAS  PubMed  Google Scholar 

  22. Özen, H. & Sözen, S. PSA isoforms in prostate cancer detection. Eur. Urol. Suppl. 5, 495–499 (2006).

    Article  CAS  Google Scholar 

  23. Peter, J., Unverzagt, C., Krogh, T. N., Vorm, O. & Hoesel, W. Identification of precursor forms of free prostate-specific antigen in serum of prostate cancer patients by immunosorption and mass spectrometry. Cancer Res. 61, 957–962 (2001).

    CAS  PubMed  Google Scholar 

  24. Nurmikko, P., Pettersson, K., Piironen, T., Hugosson, J. & Lilja, H. Discrimination of prostate cancer from benign disease by plasma measurement of intact, free prostate-specific antigen lacking an internal cleavage site at Lys145-Lys146. Clin. Chem. 47, 1415–1423 (2001).

    CAS  PubMed  Google Scholar 

  25. Lundwall, A. & Lilja, H. Molecular cloning of human prostate specific antigen cDNA. FEBS Lett. 214, 317–322 (1987).

    Article  CAS  PubMed  Google Scholar 

  26. Kumar, A., Mikolajczyk, S. D., Goel, A. S., Millar, L. S. & Saedi, M. S. Expression of pro form of prostate-specific antigen by mammalian cells and its conversion to mature, active form by human kallikrein 2. Cancer Res. 57, 3111–3114 (1997).

    CAS  PubMed  Google Scholar 

  27. Armbruster, D. A. Prostate-specific antigen: biochemistry, analytical methods, and clinical application. Clin. Chem. 39, 181–195 (1993).

    CAS  PubMed  Google Scholar 

  28. Balk, S. P., Ko, Y.-J. & Bubley, G. J. Biology of prostate-specific antigen. J. Clin. Oncol. 21, 383–391 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. Takayama, T. K., Fujikawa, K. & Davie, E. W. Characterization of the precursor of prostate-specific antigen. Activation by trypsin and by human glandular kallikrein. J. Biol. Chem. 272, 21582–21588 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Mikolajczyk, S. D. et al. A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. Urology 50, 710–714 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Vickers, A. J. & Brewster, S. F. PSA velocity and doubling time in diagnosis and prognosis of prostate cancer. Br. J. Med. Surg. Urol. 5, 162–168 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Christensson, A. et al. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J. Urol. 150, 100–105 (1993).

    Article  CAS  PubMed  Google Scholar 

  33. Catalona, W. J. et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 279, 1542–1547 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. Mikolajczyk, S. D., Marks, L. S., Partin, A. W. & Rittenhouse, H. G. Free prostate-specific antigen in serum is becoming more complex. Urology 59, 797–802 (2002).

    Article  PubMed  Google Scholar 

  35. Mikolajczyk, S. D. et al. A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. Cancer Res. 61, 6958–6963 (2001).

    CAS  PubMed  Google Scholar 

  36. Catalona, W. J. et al. Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2 to 4 ng/ml prostate specific antigen. J. Urol. 171, 2239–2244 (2004).

    Article  PubMed  Google Scholar 

  37. Sokoll, L. J. et al. A Prospective, Multicenter, National Cancer Institute Early Detection Research Network study of [-2]proPSA: Improving prostate cancer detection and correlating with cancer aggressiveness. Cancer Epidemiol. Biomarkers 19, 1193–1200 (2010).

    Article  Google Scholar 

  38. Mikolajczyk, S. D. & Rittenhouse, H. G. Pro PSA: a more cancer specific-form of prostate specific antigen for the early detection of prostate cancer. Keio J. Med. 52, 86–91 (2003).

    Article  PubMed  Google Scholar 

  39. Catalona, W. J. et al. A multi-center study of [-2]pro-prostate specific antigen (PSA) in combination with PSA and free PSA for prostate cancer detection in the 2.0 to 10.0 ng/ml PSA range. J. Urol. 185, 1650–1655 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang, W. & Leinonen, J. Purification and characterization antigen in human seminal fluid of different molecular forms of prostate-specific antigen in human seminal fluid. Clin. Chem. 41, 1567–1573 (1995).

    CAS  PubMed  Google Scholar 

  41. Mikolajczyk, S. D. et al. “BPSA” a specific molecular form of free prostate-specific antigen, is found predominantly in the transition zone of patients with nodular benign prostatic hyperplasia. Urology 55, 41–45 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Linton, H. J. et al. Benign prostate-specific antigen (BPSA) in serum is increased in benign prostate disease. Clin. Chem. 49, 253–259 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Okihara, K. et al. Comparative analysis of complexed prostate specific antigen, free prostate specific antigen and their ratio in detecting prostate cancer. J. Urol. 167, 2017–2024 (2002).

    Article  PubMed  Google Scholar 

  44. Jung, K. et al. Molecular forms of prostate-specific antigen in malignant and benign prostatic tissue: biochemical and diagnostic implications. Clin. Chem. 46, 47–54 (2000).

    CAS  PubMed  Google Scholar 

  45. Partin, A. W. et al. Complexed prostate specific antigen improves specificity for prostate cancer detection: results of a prospective multicenter clinical trial. J. Urol. 170, 1787–1791 (2003).

    Article  PubMed  Google Scholar 

  46. Varki, A. et al. Essentials of Glycobiology (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2009).

    Google Scholar 

  47. Meany, D. L. & Chan, D. W. Aberrant glycosylation associated with enzymes as cancer biomarkers. Clin. Proteomics 8, 7 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Freeze, H. H. Genetic defects in the human glycome. Nat. Rev. Genet. 7, 537–551 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Arnold, J. N., Saldova, R., Hamid, U. M. A. & Rudd, P. M. Evaluation of the serum N-linked glycome for the diagnosis of cancer and chronic inflammation. Proteomics 8, 3284–3293 (2008).

    Article  CAS  PubMed  Google Scholar 

  50. Tharmalingam, T., Mariño, K. & Rudd, P. M. Platform technology to identify potential disease markers and establish heritability and environmental determinants of the human serum N-glycome. Carbohydr. Res. 345, 1280–1282 (2010).

    Article  CAS  PubMed  Google Scholar 

  51. Lauc, G., Rudan, I., Campbell, H. & Rudd, P. M. Complex genetic regulation of protein glycosylation. Mol. Biosyst. 6, 329–335 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Kattla, J. et al. Protein glycosylation. Compr. Biotech. 3, 467–486 (2011).

    Google Scholar 

  53. Mariño, K., Bones, J., Kattla, J. J. & Rudd, P. M. A systemic approach to glycosylation analysis: a path through the maze. Nat. Chem. Biol. 6, 713–723 (2010).

    Article  CAS  PubMed  Google Scholar 

  54. Marek, K. W., Vijay, I. K. & Marth, J. D. A recessive deletion in the GlcNAc-1-phosphotransferase gene results in peri-implantation embryonic lethality. Glycobiology 9, 1263–1271 (1999).

    Article  CAS  PubMed  Google Scholar 

  55. Wu, A. M., Lisowska, E., Duk, M. & Yang, Z. Lectins as tools in glycoconjugate research. Glycoconj. J. 26, 899–913 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. Thompson, R., Creavin, A., O'Connell, M., O'Connor, B. & Clarke, P. Optimization of the enzyme-linked lectin assay for enhanced glycoprotein and glycoconjugate analysis. Anal. Biochem. 413, 114–122 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Royle, L., Radcliffe, C. M., Dwek, R. A. & Rudd, P. M. Detailed structural analysis of N-glycans released from glycoproteins in SDS-PAGE gel bands using HPLC combined with exoglycosidase array digestions. Methods Mol. Biol. 347, 125–143 (2006).

    CAS  PubMed  Google Scholar 

  58. National Institute for Bioprocessing Research and Training. Glycobase 3.1. http://glycobase.nibrt.ie/glycobase/show_nibrt.action (2012).

  59. Royle, L. et al. HPLC-based analysis of serum N-glycans on a 96-well plate platform with dedicated database software. Anal. Biochem. 376, 1–12 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Campbell, M. P., Royle, L., Radcliffe, C. M., Dwek, R. A. & Rudd, P. M. GlycoBase and autoGU: tools for HPLC-based glycan analysis. Bioinformatics 24, 1214–1216 (2008).

    Article  CAS  PubMed  Google Scholar 

  61. Lauc, G. et al. Genomics meets glycomics—the first GWAS study of human N-Glycome identifies HNF1α as a master regulator of plasma protein fucosylation. PLoS Genet. 6, e1001256 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Vitart, V. et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat. Genet. 40, 437–442 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. Bones, J., Mittermayr, S., Donoghue, N. O. & Rudd, P. M. Ultra performance liquid chromatographic profiling of serum N-glycans for fast and efficient glycosylation. Anal. Chem. 82, 10208–10215 (2010).

    Article  CAS  PubMed  Google Scholar 

  64. Tabarés, G. et al. Different glycan structures in prostate-specific antigen from prostate cancer sera in relation to seminal plasma PSA. Glycobiology 16, 132–145 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Chandrasekaran, E. V., Chawda, R., Locke, R. D., Piskorz, C. F. & Matta, K. L. Biosynthesis of the carbohydrate antigenic determinants, Globo H, blood group H, and Lewis b: a role for prostate cancer cell alpha 1, 2-L-fucosyltransferase. Glycobiology 12, 153–162 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Matsumoto, K. et al. N-glycan fucosylation of epidermal growth factor receptor modulates receptor activity and sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor. Cancer Sci. 99, 1611–1617 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Liu, Y., Yen, H. & Chen, C. Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc. Natl Acad. Sci. USA 108, 11332–11337 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Kyselova, Z. et al. Alterations in the serum glycome due to metastatic prostate cancer research articles. J. Proteome Res. 6, 1822–1832 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Saldova, R., Fan, Y., Fitzpatrick, J. M., Watson, R. W. G. & Rudd, P. M. Core fucosylation and alpha 2–3 sialylation in serum N.-glycome is significantly increased in prostate cancer comparing to benign prostate hyperplasia. Glycobiology 21, 195–205 (2011).

    Article  CAS  PubMed  Google Scholar 

  70. Peracaula, R. et al. Altered glycosylation pattern allows the distinction between prostate-specific antigen (PSA) from normal and tumor origins. Glycobiology 13, 457–470 (2003).

    Article  CAS  PubMed  Google Scholar 

  71. Ohyama, C. et al. Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy. Glycobiology 14, 671–679 (2004).

    Article  CAS  PubMed  Google Scholar 

  72. Tajiri, M., Ohyama, C. & Wada, Y. Oligosaccharide profiles of the prostate specific antigen in free and complexed forms from the prostate cancer patient serum and in seminal plasma: a glycopeptide approach. Glycobiology 18, 2–8 (2008).

    Article  CAS  PubMed  Google Scholar 

  73. Sarrats, A. et al. Differential percentage of serum prostate-specific antigen subforms suggests a new way to improve prostate cancer diagnosis. Prostate 70, 1–9 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Sarrats, A. et al. Glycan characterization of PSA 2-DE subforms from serum and seminal plasma. OMICS 14, 465–474 (2010).

    Article  CAS  PubMed  Google Scholar 

  75. Meany, D. L., Zhang, Z., Sokoll, L. J., Zhang, H. & Chan, D. W. Glycoproteomics for prostate cancer detection: changes in serum PSA glycosylation patterns. J. Proteome Res. 8, 613–619 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dwek, M. V., Jenks, A. & Leathem, A. J. C. A sensitive assay to measure biomarker glycosylation demonstrates increased fucosylation of prostate specific antigen (PSA) in patients with prostate cancer compared with benign prostatic hyperplasia. Clin. Chim. Acta 411, 1935–1939 (2010).

    Article  CAS  PubMed  Google Scholar 

  77. Meany, D. L., Hackler, L., Zhang, H. & Chan, D. W. Tyramide signal amplification for antibody-overlay lectin microarray: a strategy to improve the sensitivity of targeted glycan profiling. J. Proteome Res. 10, 1425–1431 (2011).

    Article  CAS  PubMed  Google Scholar 

  78. Vickers, A. J., Roobol, M. J. & Lilja, H. Screening for prostate cancer: early detection or overdetection? Ann. Rev. Med. 63, 161–170 (2012).

    Article  CAS  PubMed  Google Scholar 

  79. Botchorishvili, G., Matikainen, P. M. & Lilja, H. Early prostate-specific antigen changes and the diagnosis of prostate cancer. Curr. Opin. Urol. 19, 221–226 (2010).

    Article  Google Scholar 

  80. Fan, Y. et al. Applying random forests to identify biomarker panels in serum 2D-DIGE data for the detection and staging of prostate cancer. J. Proteome Res. 10, 1361–1373 (2011).

    Article  CAS  PubMed  Google Scholar 

  81. Drake, P. M. et al. Sweetening the pot; adding glycosylation to the biomarker discovery equation. Clin. Chem. 56, 223–236 (2010).

    Article  CAS  PubMed  Google Scholar 

  82. Sato, Y. et al. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N. Engl. J. Med. 328, 1082–1086 (1993).

    Article  Google Scholar 

  83. Moriwaki, K. et al. A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for increases in fucosylation. Glycobiology 17, 1311–1320 (2007).

    Article  CAS  PubMed  Google Scholar 

  84. Bradbury, A. R. M., Sidhu, S., Dübel, S. & McCafferty, J. Beyond natural antibodies: the power of in vitro display technologies. Nat. Biotech. 29, 245–254 (2011).

    Article  CAS  Google Scholar 

  85. Conroy, P. J., Hearty, S., Leonard, P. & O'Kennedy, R. J. Antibody production, design and use for biosensor-based applications. Semin. Cell Dev. Biol. 20, 10–26 (2009).

    Article  CAS  PubMed  Google Scholar 

  86. Ayyar, B. V., Hearty, S. & O'Kennedy, R. Highly sensitive recombinant antibodies capable of reliably differentiating heart-type fatty acid binding protein from noncardiac isoforms. Anal. Biochem. 407, 165–171 (2010).

    Article  CAS  PubMed  Google Scholar 

  87. Conroy, P. J., O'Kennedy, R. J. & Hearty, S. Cardiac troponin I: a case study in rational antibody design for human diagnostics. Protein Eng. Des. Sel. 25, 295–305 (2012).

    Article  CAS  PubMed  Google Scholar 

  88. Hayes, C. J., Leonard, P. & O'Kennedy, R. Overcoming antibody expression and screening limitations by smart design: Applications to PSA immunoassay development. Protein Expr. Purif. 83, 84–91 (2012).

    Article  CAS  PubMed  Google Scholar 

  89. Healy, D., Hayes, C. J., Leonard, P., McKenna, L. & O'Kennedy, R. Biosensor developments: application to prostate-specific antigen detection. Trends Biotechnol. 25, 125–131 (2007).

    Article  CAS  PubMed  Google Scholar 

  90. Thaxton, C. S. et al. Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy. Proc. Natl Acad. Sci. USA 106, 18437–18442 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Hearty, S., Leonard, P. & O'Kennedy, R. Nanomedicine: barcodes check out prostate cancer. Nat. Nanotech. 5, 9–10 (2010).

    Article  CAS  Google Scholar 

  92. Stura, E. A. et al. Crystal structure of human prostate-specific antigen in a sandwich antibody complex. J. Mol. Biol. 414, 530–544 (2011).

    Article  CAS  PubMed  Google Scholar 

  93. Muller, B. H. et al. In vitro affinity maturation of an anti-PSA antibody for prostate cancer diagnostic assay. J. Mol. Biol. 414, 545–562 (2011).

    Article  CAS  PubMed  Google Scholar 

  94. Hoeks, C. M. A. et al. Prostate cancer: multiparametric MR imaging for detection, localisation, and staging. Radiology 261, 46–62 (2011).

    Article  PubMed  Google Scholar 

  95. Oon, S. F., Pennington, S. R., Fitzpatrick, J. M. & Watson, R. W. G. Biomarker research in prostate cancer—towards utility, not futility. Nat. Rev. Urol. 8, 131–138 (2011).

    Article  CAS  PubMed  Google Scholar 

  96. Hassan, O., Ahmad, A., Sethi, S. & Sarkar, F. H. Recent updates on the role of microRNAs in prostate cancer. J. Hem. Oncol. 5, 9 (2012).

    Article  CAS  Google Scholar 

  97. Jerónimo, C. et al. Epigenetics in prostate cancer: biologic and clinical relevance. Eur. Urol. 60, 753–766 (2011).

    Article  CAS  PubMed  Google Scholar 

  98. Harvey, D. J. et al. Proposal for a standard system for drawing structural diagrams of N- and O-linked carbohydrates and related compounds. Proteomics 9, 3796–3801 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. School of Biotechnology, Dublin City University, Dublin, 9, Ireland

    Sarah Gilgunn

  2. Biomedical Diagnostics Institute, National Centre for Sensor Research, Dublin City University, Dublin, 9, Ireland

    Paul J. Conroy & Richard J. O'Kennedy

  3. NIBRT Dublin-Oxford Glycobiology Laboratory, National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Dublin, 4, Ireland

    Radka Saldova & Pauline M. Rudd

Authors
  1. Sarah Gilgunn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul J. Conroy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Radka Saldova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pauline M. Rudd
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard J. O'Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to Richard J. O'Kennedy.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2012.258

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing