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Abnormal Galactosylated–Glycans recognized by Bandeiraea Simplicifolia Lectin I in saliva of patients with breast Cancer

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Abstract

Currently, the definitive diagnosis in breast cancer requires biopsy and histopathology, such the most effective markers are tissue-based. However, the advantages of saliva in collection and storage make it possible for assessing human pathology and contributing to the development of cancer-related biomarkers for clinical application. The present study validated alteration of salivary protein glycopatterns recognized by Bandeiraea simplicifolia lectin I (BS-I) in the saliva of patients with breast diseases using saliva microarrays, and the N/O-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from 259 female subjects (66 healthy volunteers (HV), 65 benign breast cyst or tumor patients (BB), 66 patients with breast cancer in stage I (BC-I) and 62 patients with breast cancer in stage II (BC-II)) were analyzed by MALDI-TOF/TOF-MS. The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with breast cancer compared with HV (p < 0.05). Totally, there were 11/10, 10/19, 7/24 and 7/9 galactosylated N-/O-linked glycans were identified and annotated from the pooled salivary samples of HV, BB, BC-I and BC-II, respectively. One galactosylated N-glycan peak (m/z 2773.977), and 4 galactosylated O-glycan peaks (m/z 868.295, 882.243, 884.270 and 1030.348) were found only in BC-I. These findings could provide pivotal information on galactosylated N/O-linked glycans related to breast cancer, and promote the study of biomarkers for early-stage breast cancer based on precise alterations of galactosylated N/O-glycans in saliva.

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References

  1. Chen, W., Zheng, R., Baade, P.D., Zhang, S., Zeng, H., Bray, F., Jemal, A., Yu, X.Q., He, J.: Cancer statistics in China, 2015. CA Cancer J. Clin. 66(2), 115–132 (2016)

    PubMed  Google Scholar 

  2. Sturgeon, C.M., Duffy, M.J., Stenman, U.H., Lilja, H., Brünner, N., Chan, D.W., Babaian, R., Bast RC Jr, Dowell, B., Esteva, F.J., Haglund, C., Harbeck, N., Hayes, D.F., Holten-Andersen, M., Klee, G.G., Lamerz, R., Looijenga, L.H., Molina, R., Nielsen, H.J., Rittenhouse, H., Semjonow, A., Shih IeM, Sibley, P., Sölétormos, G., Stephan, C., Sokoll, L., Hoffman, B.R., Diamandis, E.P., National Academy of Clinical Biochemistry: National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin. Chem. 54(12), e11–e79 (2008)

    CAS  PubMed  Google Scholar 

  3. Smith, R.A., Andrews, K., Brooks, D., et al.: Cancer screening in the United States, 2016: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J. Clin. 66(2), 69–114 (2016)

    CAS  Google Scholar 

  4. Marmot, M.G., Altman, D.G., Cameron, D.A., Dewar, J.A., Thompson, S.G., Wilcox, M.: The benefits and harms of breast cancer screening: an independent review. Br. J. Cancer. 108(11), 2205–2240 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Corbex, M., Burton, R., Sancho-Garnier, H.: Breast cancer early detection methods for low and middle income countries, a review of the evidence. Breast. 21(4), 428–434 (2012)

    PubMed  Google Scholar 

  6. Ohtsubo, K., Marth, J.D.: Glycosylation in cellular mechanisms of health and disease. Cell. 126(5), 855–867 (2006)

    CAS  PubMed  Google Scholar 

  7. Lebrilla, C.B., An, H.J.: The prospects of glycan biomarkers for the diagnosis of diseases. Mol. BioSyst. 5(1), 17–20 (2009)

    CAS  PubMed  Google Scholar 

  8. Pinho, S.S., Reis, C.A.: Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer. 15(19), 540–555 (2015)

    CAS  PubMed  Google Scholar 

  9. Kaur, S., Kumar, S., Momi, N., et al.: Mucins in pancreatic cancer and its microenvironment. Nat Rev Gastroenterol Hepatol. 10(10), 607–620 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Drake, R.R.: Glycosylation and cancer: moving glycomics to the forefront. Adv. Cancer Res. 126, 1–10 (2015)

    CAS  PubMed  Google Scholar 

  11. RodrÍguez, E., Schetters, S.T.T., van Kooyk, Y.: The tumour glyco-code as a novel immune checkpoint for immunotherapy. Nat Rev Immunol. 18(3), 204–211 (2018)

    PubMed  Google Scholar 

  12. Sun, S., Shah, P., Eshgh, S.T., et al.: Comprehensive analysis of protein glycosylation by solid-phase extraction of N-linked glycans and glycosite-containing peptides. Nat Biotechnol. 34(1), 84–88 (2016)

    CAS  PubMed  Google Scholar 

  13. Calafat, J., Janssen, H.: Binding of lectins to human mammary tumors: ultrastructural study. Breast Cancer Res Tr. 4(3), 169–179 (1984)

    CAS  Google Scholar 

  14. Springer, G.F.: Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. J. Mol. Med. 75(8), 594–602 (1997)

    CAS  PubMed  Google Scholar 

  15. Burchell, J., Durbin, H., Taylor-Papadimitriou, J.: Complexity of expression of antigenic eterminants, recognized by monoclonal antibodies HMFG-1 and HMFG-2, in normal and malignant human mammary epithelial cells. J. Immunol. 131(1), 508–513 (1983)

    CAS  PubMed  Google Scholar 

  16. Jeschke, U.: Can we find breast Cancer via salivary fluid glycosylation analyses? EbioMedicine. 28, 4 (2018)

    PubMed  PubMed Central  Google Scholar 

  17. Gillece-Castro, B.L., Prakobphol, A., Burlingame, A.L., et al.: Structure and bacterial receptor activity of a human salivary proline-rich glycoprotein. J. Biol. Chem. 266(26), 17358–17368 (1991)

    CAS  PubMed  Google Scholar 

  18. Paige, S.Z., Streckfus, C.F.: Salivary analysis in the diagnosis and treatment of breast cancer: a role for the general dentist. Gen. Dent. 55(2), 156–157 (2017)

    Google Scholar 

  19. Ozturk, L.K., Emekli-Alturfan, E., Kasikci, E., et al.: Salivary total sialic acid levels increase in breast cancer patients: a preliminary study. Med. Chem. 7(5), 443–447 (2011)

    CAS  PubMed  Google Scholar 

  20. Scott, D.A., Casadonte, R., Cardinali, B., Spruill, L., Mehta, A.S., Carli, F., Simone, N., Kriegsmann, M., del Mastro, L., Kriegsmann, J., Drake, R.R.: Increases in tumor N-glycan Polylactosamines associated with advanced HER2-positive and triple-negative breast Cancer tissues. Proteomics Clin Appl. 13(1), e1800014 (2019)

    PubMed  Google Scholar 

  21. Liu, X., Yu, H., Qiao, Y., Yang, J., Shu, J., Zhang, J., Zhang, Z., He, J., Li, Z.: Salivary Glycopatterns as potential biomarkers for screening of early-stage breast Cancer. EbioMedicine. 28, 70–79 (2018)

    PubMed  PubMed Central  Google Scholar 

  22. Kisailus, E.C., Kabat, E.A.: A study of the specificity of Bandeiraea simplicifolia lectin I by competitive-binding assay with blood-group substances and with blood-group a and B active and other oligosaccharides. Carbohydr. Res. 67(1), 243–255 (1978)

    CAS  PubMed  Google Scholar 

  23. Wu, A.M., Song, S.C., Wu, J.H., et al.: Affinity of Bandeiraea (Griffonia) simplicifolia lectin-I, isolectin B4 for Gal alpha 1–4 Gal ligand. Biochem Biophys Res Commun. 216(3), 814–820 (1995)

    CAS  PubMed  Google Scholar 

  24. Qin, Y., Zhong, Y., Zhu, M., Dang, L., Yu, H., Chen, Z., Chen, W., Wang, X., Zhang, H., Li, Z.: Age- and sex-associated differences in the glycopatterns of human salivary glycoproteins and their roles against influenza a virus. J. Proteome Res. 12(6), 2742–2754 (2013)

    CAS  PubMed  Google Scholar 

  25. Zhang, J., Zhong, Y., Zhang, P., du, H., Shu, J., Liu, X., Zhang, H., Guo, Y., Jia, Z., Niu, L., Yang, F., Li, Z.: Identification of abnormal Fucosylated-Glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Glycobiology. 29(3), 242–259 (2019)

    CAS  PubMed  Google Scholar 

  26. Yang, G., Cui, T., Wang, Y., Sun, S., Ma, T., Wang, T., Chen, Q., Li, Z.: Selective isolation and analysis of glycoprotein fractions and their glycomes from hepatocellular carcinoma sera. Proteomics. 13(9), 1481–1498 (2013)

    CAS  PubMed  Google Scholar 

  27. Yang, G., Cui, T., Chen, Q., Ma, T., Li, Z.: Isolation and identification of native membrane glycoproteins from living cell by Concanavalin A-magnetic particle conjugates. Anal. Biochem. 421(1), 339–341 (2012)

    CAS  PubMed  Google Scholar 

  28. Qin, Y., Zhong, Y., Ma, T., et al.: A pilot study of salivary N-glycome in HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Glycoconj. J. 34(4), 523–535 (2016)

    Google Scholar 

  29. Song, X., Ju, H., Lasanajak, Y., Kudelka, M.R., Smith, D.F., Cummings, R.D.: Oxidative release of natural glycans for functional glycomics. Nat. Methods. 13(6), 528–534 (2016)

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Ranzinger, R., York, W.S.: GlycomeDB. Methods Mol Biol. 1273, 109–124 (2014)

    Google Scholar 

  31. Damerell, D., Ceroni, A., Maass, K., et al.: Annotation of glycomics MS and MS/MS spectra using the GlycoWorkbench software tool. Methods Mol. Biol. 1273, 3–15 (2015)

    CAS  PubMed  Google Scholar 

  32. Varki, A., Cummings, R.D., Aebi, M., et al.: Symbol nomenclature for graphical representations of glycans. Glycobiology. 25(12), 1323–1324 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Sh Ju, Y.H., Du, H., et al.: Identification of N- and O-linked glycans recognized by AAL in saliva of patients with atrophic gastritis and gastric cancer. Cancer Biomark. 22(4), 669–681 (2018)

    Google Scholar 

  34. Brooks, S.A., Leathem, A.J.: Expression of alpha-GalNAc glycoproteins by breast cancers. Br. J. Cancer. 71(5), 1033–1038 (1995)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Lomax-Browne, H.J., Robertson, C., Antonopoulos, A., Leathem, A.J.C., Haslam, S.M., Dell, A., Dwek, M.V.: Serum IgA1 shows increased levels of α2,6-linked sialic acid in breast cancer. Interface Focus. 9(2), 20180079 (2019)

    PubMed  PubMed Central  Google Scholar 

  36. Plomp, R., de Haan, H., Bondt, A., et al.: Comparative Glycomics of immunoglobulin a and G from saliva and plasma reveals biomarker potential. Front. Immunol. 9, 2436 (2019)

    Google Scholar 

  37. Parekh, R.B., Dwek, R.A., Sutton, B.J., Fernandes, D.L., Leung, A., Stanworth, D., Rademacher, T.W., Mizuochi, T., Taniguchi, T., Matsuta, K.: Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature. 316(6027), 452–457 (1985)

    CAS  PubMed  Google Scholar 

  38. Martin, K., Talukder, R., Hay, F.C., et al.: Characterization of changes in IgG associated oligosaccharide profiles in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis using fluorophore linked carbohydrate electrophoresis. J Rheumatol. 28(7), 1531–1536 (2001)

    CAS  PubMed  Google Scholar 

  39. Ren, S., Zhang, Z., Xu, C., Guo, L., Lu, R., Sun, Y., Guo, J., Qin, R., Qin, W., Gu, J.: Distribution of IgG galactosylation as a promising biomarker for cancer screening in multiple cancer types. Cell Res. 26(8), 963–966 (2016)

    PubMed  PubMed Central  Google Scholar 

  40. Axford, J.S., Sumar, N., Alavi, A., Isenberg, D.A., Young, A., Bodman, K.B., Roitt, I.M.: Changes in normal glycosylation mechanisms in autoimmune rheumatic disease. J. Clin. Invest. 89(3), 1021–1031 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Bones, J., Byrne, J.C., O'Donoghue, N., McManus, C., Scaife, C., Boissin, H., Nastase, A., Rudd, P.M.: Glycomic and glycoproteomic analysis of serum from patients with stomach cancer reveals potential markers arising from host defense response mechanisms. J. Proteome Res. 10(3), 1246–1265 (2011)

    CAS  PubMed  Google Scholar 

  42. Kolarich, D., Rapp, E., Struwe, W.B., Haslam, S.M., Zaia, J., McBride, R., Agravat, S., Campbell, M.P., Kato, M., Ranzinger, R., Kettner, C., York, W.S.: The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting mass-spectrometry-based glycoanalytic data. Mol. Cell. Proteomics. 12(4), 991–995 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  43. York, W.S., Agravat, S., Aokikinoshita, K.F., et al.: Mirage: the minimum information required for a glycomics experiment. Glycobiology. 24(5), 402–406 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Guile, G.R., Harvey, D.J., O'Donnell, N., Powell, A.K., Hunter, A.P., Zamze, S., Fernandes, D.L., Dwek, R.A., Wing, D.R.: Identification of highly fucosylated N-linked oligosaccharides from the human parotid gland. Eur. J. Biochem. 258(2), 623–656 (1998)

    CAS  PubMed  Google Scholar 

  45. Marino, K., Saldova, R., Adamczyk, B., et al.: Changes in serum N-glycosylation profiles: functional significance and potential for diagnostics. Carbohydr. Chem. 37, 57–93 (2012)

    CAS  Google Scholar 

  46. Saldova, R., Asadi Shehni, A., Haakensen, V.D., et al.: Association of N-glycosylation with breast carcinoma and systemic features using high-resolution quantitative UPLC. J Proteome Res. 13(5), 2314–2327 (2014)

    CAS  PubMed  Google Scholar 

  47. Christiansen, M.N., Chik, J., Lee, L., Anugraham, M., Abrahams, J.L., Packer, N.H.: Cell surface protein glycosylation in cancer. Proteomics. 14(4–5), 525–546 (2014)

    CAS  PubMed  Google Scholar 

  48. Arnold, J.N., Saldova, R., Hamid, U.M., Rudd, P.M.: Evaluation of the serum N-linked glycome for the diagnosis of cancer and chronic inflammation. Proteomics. 8(16), 3284–3293 (2008)

    CAS  PubMed  Google Scholar 

  49. Pinho, S.S., Reis, C.A.: Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer. 15(9), 540–555 (2015)

    CAS  PubMed  Google Scholar 

  50. Kim, Y.J., Varki, A.: Perspectives on the significance of altered glycosylation of glycoproteins in cancer. Glycoconj. J. 14(5), 569–576 (1997)

    CAS  PubMed  Google Scholar 

  51. Munkley, J.: The role of Sialyl-Tn in Cancer. Int. J. Mol. Sci. 17(3), 275 (2016)

    PubMed  PubMed Central  Google Scholar 

  52. Kannagi, R., Yin, J., Miyazaki, K., et al.: Current relevance of incomplete synthesis and neo-synthesis for cancer-associated alteration of carbohydrate determinants—Hakomori’s concepts revisited. Biochim. Biophys. Acta. 1780(3), 525–531 (2008)

    CAS  PubMed  Google Scholar 

  53. Gill, D.J., Chia, J., Senewiratne, J., Bard, F.: Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes. J. Cell Biol. 189(5), 843–858 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Pinho, S.S., Reis, C.A.: Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer. 15(9), 540–555 (2015)

    CAS  PubMed  Google Scholar 

  55. Hakomori, S., Kannagi, R.: Glycosphingolipids as tumor-associated and differentiation markers. J. Natl. Cancer Inst. 71(2), 231–251 (1983)

    CAS  PubMed  Google Scholar 

  56. Marcos, N.T., Bennett, E.P., Gomes, J., et al.: ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues. Front. Biosci. (Elite Ed). 3(1443–1455), (2011)

  57. Julien, S., Adriaenssens, E., Ottenberg, K., Furlan, A., Courtand, G., Vercoutter-Edouart, A.S., Hanisch, F.G., Delannoy, P., le Bourhis, X.: ST6GalNAc I expression in MDA-MB-231 breast cancer cells greatly modifies their O-glycosylation pattern and enhances their tumourigenicity. Glycobiology. 16(1), 54–64 (2006)

    CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (81372365).

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  1. Jiajun Yang and Xiawei Liu contributed equally to this work.

Authors and Affiliations

  1. Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi’an, 710069, China

    Jiajun Yang, Xiawei Liu, Jian Shu, Yao Hou, Mengting Chen, Hanjie Yu, Tianran Ma, Haoqi Du, Jiaxu Zhang & Zheng Li

  2. Department of Surgical Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Yan Qiao & Jianjun He

  3. Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, Institution of Biophysics, Chinese Academy of Sciences, Beijing, China

    Lili Niu & Fuquan Yang

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  1. Jiajun Yang
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Contributions

JY, XL and ZL designed research; JY, LX, HY, JS, MC, HD, JZ, YQ, JH, LN, TM, YH and FY performed research; JY, XL and ZL analyzed data; JY, XL and ZL wrote the paper.

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Yang, J., Liu, X., Shu, J. et al. Abnormal Galactosylated–Glycans recognized by Bandeiraea Simplicifolia Lectin I in saliva of patients with breast Cancer. Glycoconj J 37, 373–394 (2020). https://doi.org/10.1007/s10719-020-09910-6

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