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Analysis of serum glycome by lectin microarrays for prostate cancer patients - a search for aberrant glycoforms

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Abstract

This is the first work focused on glycoprofiling of whole N- and O- glycome using lectins in an array format applied for analysis of serum samples from healthy individuals, benign prostate hyperplasia (BPH) patients, and prostate cancer (PCa) patients. Lectin microarray was prepared using traditional lectins with the incorporation of 2 recombinant bacterial lectins and 3 human lectins (17 lectins in total). Clinical validation of glycans as biomarkers was done in two studies: discrimination of healthy individuals with BPH patients vs. PCa patients (C vs. PCa) and discrimination of healthy individuals vs. BPH and PCa patients (H vs. PCond). Single lectins (17 lectins) and a combination of two lectins (136 binary lectin combinations) were applied in the clinical validation of glycan biomarkers providing 153 AUC values from ROC curves for both studies (C vs. PCa and H vs. PCond). Potential N- and O-glycans as biomarkers were identified and possible carriers of these glycans are shortly discussed.

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References

  1. Collaboration, G.B.o.D.C.: Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: A systematic analysis for the global burden of disease study. JAMA Oncol. 5(12), 1749–1768 (2019). https://doi.org/10.1001/jamaoncol.2019.2996

  2. O’Reilly, J.-A., O’Kennedy, R.J.: Prostate cancer detection: complexities and strategies. J. Cancer Treat. Diagn. 2(1), 18–25 (2017)

    Article  Google Scholar 

  3. Tkac, J., Bertok, T., Hires, M., Jane, E., Lorencova, L., Tkac, J., Bertok, T., Lorencova, L., Kasak, P.: Glycomics of prostate cancer: updates. Exp. Rev. Proteomics. 16(1), 65–76 (2019). https://doi.org/10.1080/14789450.2019.1549993. Accessed 20 Mar 2020

  4. Tkac, J., Gajdosova, V., Hroncekova, S., Bertok, T., Hires, M., Jane, E., Lorencova, L., Kasak, P.: Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer. Interface Focus 9(2), ID: 20180077: (2019). https://doi.org/10.1098/rsfs.2018.0077

  5. Rodríguez, J.Z., O’Kennedy, R.: New approaches for the develoment of diagnostic systems for prostate cancer. Asian Hosp. Healthc. Manag., 18–23 (2017)

  6. Garnick, M.B., Abrahamsson, P.-A., Dewolf, W.C., Kacker, R., Kaplan, I., Louglin, K.R., Srougi, M., Sternberg, C.N., Zietman, A.L.: Harvard Medical School 2018 Annual report on prostate diseases. Harvard, US: Harvard Medical School. Harvard Health Publishing, Boston (2018)

  7. Ablin, R.J., Piana, R.: The great prostate hoax: How big medicine hijacked the PSA test and caused a public health disaster. Palgrave McMillian, New York (2014)

    Google Scholar 

  8. Ablin, R.J.: Prostate cancer test has been misused for money. https://www.newscientist.com/article/mg22129564-400-prostate-cancer-test-has-been-misused-for-money/ (2014)

  9. Moyer, V.A.: Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann. Intern. Med. 157(2), 120–134 (2012). https://doi.org/10.7326/0003-4819-157-2-201207170-00459

    Article  PubMed  Google Scholar 

  10. Van Der Kwast, T.H., Roobol, M.J.: Prostate cancer: Draft USPSTF 2017 recommendation on PSA testing-a sea-change? Nat. Rev. Urol. 14(8), 457–458 (2017). https://doi.org/10.1038/nrurol.2017.89

    Article  PubMed  Google Scholar 

  11. Grossman, D.C., Curry, S.J., Owens, D.K., Bibbins-Domingo, K., Caughey, A.B., Davidson, K.W., Doubeni, C.A., Ebell, M., Epling, J.W. Jr., Kemper, A.R., Krist, A.H., Kubik, M., Landefeld, C.S., Mangione, C.M., Silverstein, M., Simon, M.A., Siu, A.L., Tseng, C.-W.: Screening for prostate cancer: Us preventive services task force recommendation statement. JAMA. 319(18), 1901–1913 (2018). https://doi.org/10.1001/jama.2018.3710

    Article  PubMed  Google Scholar 

  12. Fleshner, K., Carlsson, S.V., Roobol, M.J.: The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA. Nat. Rev. Urol. 14(1), 26–37 (2017). https://doi.org/10.1038/nrurol.2016.251

    Article  CAS  PubMed  Google Scholar 

  13. Early Detection of Prostate Cancer, American Urological Association (AUA) Guideline. https://www.auanet.org/Documents/Guidelines/PDF/EarlyProstateCancerGuideline_71318%20PDF.pdf (2018). Accessed 16 Mar 2020

  14. Sharma, S., Zapatero-Rodríguez, J., O’Kennedy, R.: Prostate cancer diagnostics: Clinical challenges and the ongoing need for disruptive and effective diagnostic tools. Biotechnol. Adv. 35(2), 135–149 (2017). https://doi.org/10.1016/j.biotechadv.2016.11.009

    Article  PubMed  Google Scholar 

  15. Kohaar, I., Petrovics, G., Srivastava, S.: A rich array of prostate cancer molecular biomarkers: opportunities and challenges. Int. J. Mol. Sci. 20(8), 1813 (2019). https://doi.org/10.3390/ijms20081813

    Article  CAS  PubMed Central  Google Scholar 

  16. Cohen, J.D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A.A., Wong, F., Mattox, A.: Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science, eaar3247 (2018). https://doi.org/10.1126/science.aar3247

  17. Murphy, K., Murphy, B.T., Boyce, S., Flynn, L., Gilgunn, S., O’Rourke, C.J., Rooney, C., Stöckmann, H., Walsh, A.L., Finn, S., O’Kennedy, R.J., O’Leary, J., Pennington, S.R., Perry, A.S., Rudd, P.M., Saldova, R., Sheils, O., Shields, D.C., Watson, R.W.: Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer. Mol. Oncol. 12(9), 1513–1525 (2018). https://doi.org/10.1002/1878-0261.12348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ferrer-Batallé, M., Llop, E., Ramírez, M., Aleixandre, R.N., Saez, M., Comet, J., De Llorens, R., Peracaula, R.: Comparative study of blood-based biomarkers, α2, 3-sialic acid PSA and PHI, for high-risk prostate cancer detection. Int. J. Mol. Sci. 18(4), 845 (2017)

    Article  Google Scholar 

  19. Llop, E., Ferrer-Batalle, M., Barrabes, S., Enrique Guerrero, P., Ramirez, M., Saldova, R., Rudd, P.M., Aleixandre, R.N., Comet, J., de Llorens, R., Peracaula, R.: Improvement of prostate cancer diagnosis by detecting PSA glycosylation-specific changes. Theranostics 6(8), 1190–1204 (2016). https://doi.org/10.7150/thno.15226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Saldova, R., Fan, Y., Fitzpatrick, J.M., Watson, R.W.G., Rudd, P.M.: Core fucosylation and α2–3 sialylation in serum N-glycome is significantly increased in prostate cancer comparing to benign prostate hyperplasia. Glycobiology. 21(2), 195–205 (2011). https://doi.org/10.1093/glycob/cwq147

    Article  CAS  PubMed  Google Scholar 

  21. Li, Y., Tao, S.-C., Bova, G.S., Liu, A.Y., Chan, D.W., Zhu, H., Zhang, H.: Detection and verification of glycosylation patterns of glycoproteins from clinical specimens using lectin microarrays and lectin-based immunosorbent assays. Anal. Chem. 83(22), 8509–8516 (2011). https://doi.org/10.1021/ac201452f

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zamorova, M., Holazova, A., Miljus, G., Robajac, D., Sunderic, M., Malenkovic, V., Dukanovic, B., Gemeiner, P., Katrlik, J., Nedic, O.: Analysis of changes in the glycan composition of serum, cytosol and membrane glycoprotein biomarkers of colorectal cancer using a lectin-based protein microarray. Anal. Methods. 9(18), 2660–2666 (2017). https://doi.org/10.1039/c7ay00159b

    Article  CAS  Google Scholar 

  23. Fry, S.A., Afrough, B., Lomax-Browne, H.J., Timms, J.F., Velentzis, L.S., Leathem, A.J.C.: Lectin microarray profiling of metastatic breast cancers. Glycobiology. 21(8), 1060–1070 (2011). https://doi.org/10.1093/glycob/cwr045

    Article  CAS  PubMed  Google Scholar 

  24. Beauharnois, M.E., Lindquist, K.C., Marathe, D., Vanderslice, P., Xia, J., Matta, K.L., Neelamegham, S.: Affinity and kinetics of sialyl Lewis-X and core-2 based oligosaccharides binding to L-and P-selectin. Biochemistry. 44(27), 9507–9519 (2005). https://doi.org/10.1021/bi0507130

    Article  CAS  PubMed  Google Scholar 

  25. Team, R.C.: R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna (2017). https://www.R-project.org. Accessed 3 June 2020

  26. Venables, W.N., Ripley, B.D.: Modern applied statistics with S, 4th edn. Springer, New York (2002)

  27. Sing, T., Sander, O., Beerenwinkel, N., Lengauer, T.: ROCR: visualizing classifier performance in R. Bioinformatics 21(20), 7881 (2005)

  28. Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J., Müller, M.: pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12, 77 (2011)

  29. Carpenter, J., Bithell, J.: Bootstrap confidence intervals: when, which, what? A practical guide for medical statisticians. Stat. Med. 19(9), 1141–1164 (2000)

    Article  CAS  Google Scholar 

  30. Ström, P., Nordström, T., Aly, M., Egevad, L., Grönberg, H., Eklund, M.: The Stockholm-3 model for prostate cancer detection: algorithm update, biomarker contribution, and reflex test potential. Eur. Urol. 74(2), 204–210 (2018)

    Article  Google Scholar 

  31. Pinho, S.S., Reis, C.A.: Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer. 15, 540–555 (2015). https://doi.org/10.1038/nrc3982

    Article  CAS  PubMed  Google Scholar 

  32. Tkac, J., Bertok, T., Hires, M., Jane, E., Lorencova, L., Kasak, P.: Glycomics of prostate cancer: updates. Exp. Rev. Proteomics. (2018). https://doi.org/10.1080/14789450.2019.1549993

    Article  Google Scholar 

  33. Stowell, S.R., Ju, T., Cummings, R.D.: Protein glycosylation in cancer. In: Abbas, A.K., Galli, S.J., Howley, P.M. (eds.) Annual review of pathology: Mechanisms of disease, vol 10. Annual review of pathology-mechanisms of disease, pp. 473–510 (2015)

  34. Teoh, S.T., Ogrodzinski, M.P., Ross, C., Hunter, K.W., Lunt, S.Y.: Sialic acid metabolism: A key player in breast cancer metastasis revealed by metabolomics. Front. Oncol. 8(174) (2018). https://doi.org/10.3389/fonc.2018.00174

  35. Blanas, A., Sahasrabudhe, N.M., Rodríguez, E., van Kooyk, Y., van Vliet, S.J.: Fucosylated antigens in cancer: An alliance toward tumor progression, metastasis, and resistance to chemotherapy. Front. Oncol. 8(39) (2018). https://doi.org/10.3389/fonc.2018.00039

  36. Hirabayashi, J., Yamada, M., Kuno, A., Tateno, H.: Lectin microarrays: concept, principle and applications. Chem. Soc. Rev. 42(10), 4443–4458 (2013). https://doi.org/10.1039/C3CS35419A

    Article  CAS  PubMed  Google Scholar 

  37. Cummings, R.D., Darvill, A.G., Etzler, M.E., G., H.M.: Glycan-recognizing probes as tools. In: Varki, A., Cummings, R., Esko, J. (eds.) Essentials of glycobiology [Internet]. 3rd edition, pp. 2015–2017. Cold Spring Harbor Laboratory Press, Cold Spring Harbor (2017)

  38. Houser, J., Komarek, J., Kostlanova, N., Cioci, G., Varrot, A., Kerr, S.C., Lahmann, M., Balloy, V., Fahy, J.V., Chignard, M., Imberty, A., Wimmerova, M.: A soluble fucose-specific lectin from Aspergillus fumigatus conidia - structure, specificity and possible role in fungal pathogenicity. PLoS One. 8(12), e83077/83071-e83077/83015, 83015 pp (2013). https://doi.org/10.1371/journal.pone.0083077

  39. Ruhl, S., Sandberg, A.L., Cole, M.F., Cisar, J.O.: Recognition of immunoglobulin A1 by oral actinomyces and streptococcal lectins. Infect. Immun. 64(12), 5421–5424 (1996). https://doi.org/10.1128/iai.64.12.5421-5424.1996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Läubli, H., Borsig, L.: Selectins promote tumor metastasis. Semin. Cancer Biol. 20(3), 169–177 (2010). https://doi.org/10.1016/j.semcancer.2010.04.005

    Article  CAS  PubMed  Google Scholar 

  41. Shimomura, M., Nakayama, K., Azuma, K., Terao, N., Nishino, K., Takamatsu, S., Nakano, M., Takahashi, S., Kobayashi, Y., Murata, K., Kamada, Y., Miyoshi, E.: Establishment of a novel lectin-antibody ELISA system to determine core-fucosylated haptoglobin. Clin. Chim. Acta. 446, 30–36 (2015). https://doi.org/10.1016/j.cca.2015.03.037

    Article  CAS  PubMed  Google Scholar 

  42. de Vroome, S.W., Holst, S., Girondo, M.R., van der Burgt, Y.E.M., Mesker, W.E., Tollenaar, R.A.E.M., Wuhrer, M.: Serum N -glycome alterations in colorectal cancer associate with survival. Oncotarget 9(55) (2018). https://doi.org/10.18632/oncotarget.25753

  43. Matsumoto, T., Hatakeyama, S., Yoneyama, T., Tobisawa, Y., Ishibashi, Y., Yamamoto, H., Yoneyama, T., Hashimoto, Y., Ito, H., Nishimura, S.-I., Ohyama, C.: Serum N-glycan profiling is a potential biomarker for castration-resistant prostate cancer. Sci. Rep. 9(1), 16761 (2019). https://doi.org/10.1038/s41598-019-53384-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. van de Bovenkamp, F.S., Hafkenscheid, L., Rispens, T., Rombouts, Y.: The emerging importance of IgG Fab glycosylation in immunity. J. Immunol. 196(4), 1435–1441 (2016). https://doi.org/10.4049/jimmunol.1502136

    Article  CAS  PubMed  Google Scholar 

  45. Kinoshita, N., Ohno, M., Nishiura, T., Fujii, S., Nishikawa, A., Kawakami, Y., Uozumi, N., Taniguchi, N.: Glycosylation at the Fab portion of myeloma immunoglobulin G and increased fucosylated biantennary sugar chains: structural analysis by high-performance liquid chromatography and antibody-lectin enzyme immunoassay using Lens culinaris agglutinin. Cancer Res. 51(21), 5888–5892 (1991)

    CAS  PubMed  Google Scholar 

  46. Epp, A., Sullivan, K.C., Herr, A.B., Strait, R.T.: Immunoglobulin glycosylation effects in allergy and immunity. Curr. Alergy Asthma Rep. 16(11), 1–13 (2016). https://doi.org/10.1007/s11882-016-0658-x

    Article  CAS  Google Scholar 

  47. Kazuno, S., Murayama, K., Ueno, T., Fujimura, T., Furukawa, J.-I., Shinohara, Y., Fujime, M.: Glycosylation status of serum immunoglobulin G in patients with prostate diseases. Cancer Med. 5(6), 1137–1146 (2016). https://doi.org/10.1002/cam4.662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Saldova, R., Royle, L., Radcliffe, C.M., Abd Hamid, U.M., Evans, R., Arnold, J.N., Banks, R.E., Hutson, R., Harvey, D.J., Antrobus, R., Petrescu, S.M., Dwek, R.A., Rudd, P.M.: Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG. Glycobiology 17(12), 1344–1356 (2007). https://doi.org/10.1093/glycob/cwm100

    Article  CAS  PubMed  Google Scholar 

  49. Kodar, K., Stadlmann, J., Klaamas, K., Sergeyev, B., Kurtenkov, O.: Immunoglobulin G Fc N-glycan profiling in patients with gastric cancer by LC-ESI-MS: relation to tumor progression and survival. Glycoconjugate J. 29(1), 57–66 (2012). https://doi.org/10.1007/s10719-011-9364-z

    Article  CAS  Google Scholar 

  50. Gebrehiwot, A.G., Melka, D.S., Kassaye, Y.M., Gemechu, T., Lako, W., Hinou, H., Nishimura, S.-I.: Exploring serum and immunoglobulin G N-glycome as diagnostic biomarkers for early detection of breast cancer in Ethiopian women. BMC Cancer. 19(1), 588 (2019). https://doi.org/10.1186/s12885-019-5817-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Vučković, F., Theodoratou, E., Thaçi, K., Timofeeva, M., Vojta, A., Štambuk, J., Pučić-Baković, M., Rudd, P.M., Đerek, L., Servis, D., Wennerström, A., Farrington, S.M., Perola, M., Aulchenko, Y., Dunlop, M.G., Campbell, H., Lauc, G.: IgG glycome in colorectal cancer. Clin. Cancer Res. 22(12), 3078–3086 (2016). https://doi.org/10.1158/1078-0432.Ccr-15-1867

    Article  PubMed  PubMed Central  Google Scholar 

  52. Doherty, M., Theodoratou, E., Walsh, I., Adamczyk, B., Stockmann, H., Agakov, F., Timofeeva, M., Trbojevic-Akmacic, I., Vuckovic, F., Duffy, F., McManus, C.A., Farrington, S.M., Dunlop, M.G., Perola, M., Lauc, G., Campbell, H., Rudd, P.M.: Plasma N-glycans in colorectal cancer risk. Sci. Rep. 8(1), 1–12 (2018). https://doi.org/10.1038/s41598-018-26805-7

    Article  CAS  Google Scholar 

  53. Yu, H., Shu, J., Li, Z.: Lectin microarrays for glycoproteomics: an overview of their use and potential. Exp. Rev. Proteomics. 17(1), 27–39 (2020). https://doi.org/10.1080/14789450.2020.1720512

    Article  CAS  Google Scholar 

  54. de Haan, N., Falck, D., Wuhrer, M.: Monitoring of immunoglobulin N- and O-glycosylation in health and disease. Glycobiology.(2020). https://doi.org/10.1093/glycob/cwz1048

    Article  PubMed  Google Scholar 

  55. Plomp, R., de Haan, N., Bondt, A., Murli, J., Dotz, V., Wuhrer, M.: Comparative glycomics of immunoglobulin A and G from saliva and plasma reveals biomarker potential. Front. Immunol. 9, 2436/2431–2436/2412 (2018). https://doi.org/10.3389/fimmu.2018.02436

    Article  CAS  Google Scholar 

  56. Hatakeyama, S., Yoneyama, T., Tobisawa, Y., Ohyama, C.: Recent progress and perspectives on prostate cancer biomarkers. Int. J. Clin. Oncol. 22(2), 214–221 (2017)

    Article  CAS  Google Scholar 

  57. Chen, S., LaRoche, T., Hamelinck, D., Bergsma, D., Brenner, D., Simeone, D., Brand, R.E., Haab, B.B.: Multiplexed analysis of glycan variation on native proteins captured by antibody microarrays. Nat. Methods. 4(5), 437–444 (2007). https://doi.org/10.1038/nmeth1035

    Article  CAS  PubMed  Google Scholar 

  58. Lauc, G., Pezer, M., Rudan, I., Campbell, H.: Mechanisms of disease: The human N-glycome. Biochim. Biophys. Acta-Gen. Subj. 1860(8), 1574–1582 (2016). https://doi.org/10.1016/j.bbagen.2015.10.016

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the financial support received from VEGA 2/0130/20 and the Slovak Research and Development Agency APVV 17–0300 and APVV-15-0227. We would like to acknowledge the support received from the Ministry of Health of the Slovak Republic under the project registration number 2019/68-CHÚSAV-1. This publication was supported by Qatar University Grants IRCC-2020-004. The statements made herein are solely the responsibility of the authors. This publication was created with the support of the Operational Program Integrated Infrastructure for the project: Center for Biomedical Research - BIOMEDIRES - II. stage, ITMS: 313011W428, co-financed by the European Regional Development Fund.

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Bertok, T., Jane, E., Chrenekova, N. et al. Analysis of serum glycome by lectin microarrays for prostate cancer patients - a search for aberrant glycoforms. Glycoconj J 37, 703–711 (2020). https://doi.org/10.1007/s10719-020-09958-4

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