Changes of serum protein N-glycosylation in cancer

Česká verzia

Authors: I. Benešová ¹; A. Paulin Urminský ¹; J. Halámková ²; L. Hernychová ¹
Authors place of work: Výzkumné centrum aplikované molekulární onkologie, MOÚ, Brno ¹; Klinika komplexní onkologické péče LF MU a MOÚ, Brno ²
Published in the journal: Klin Onkol 2022; 35(3): 174-180
Category: Review
doi: https://doi.org/10.48095/ccko2022174

Summary

Background: Glycosylation is a posttranslational modification responsible for many biological processes including protein-protein interactions, cell signaling or cell cycle regulation. Changes in glycosylation of serum proteins reflects the status of tissues and cells in the organism and therefore can be used as markers for diagnosis of cancer, its progression and determination of its subtypes. N-glycan profiling is often used for characterization of N-glycosylation changes. It is based on the measurements of N-glycans released from the serum proteins. Beside the N-glycan profiling, glycoproteomic approach is emerging as it preserves the information about glycan composition, original protein, and its glycosylation sites. Purpose: This review covers existing works describing the changes in serum protein N-glycosylation in various cancer types. Attention was paid to both the glycomic and glycoproteomic approaches. The last part of the review shortly presents the analytical methods used for these analyses.

Keywords:

Serum proteins – Mass spectrometry – glycomics – glycoproteomics – N-glycans – N-glycan profiling – glycopeptides

Zdroje

1. Reily C, Stewart TJ, Renfrow MB et al. Glycosylation in health and disease. Nat Rev Nephrol 2019; 15 (6): 346–366. doi: 10.1038/s41581-019-0129-4.

2. Colley KJ, Varki AK. Cellular organization of glycosylation. In: Varki A. (ed). Essentials of glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press 2017.

3. Ho WL, Hsu WM, Huang MC et al. Protein glycosylation in cancers and its potential therapeutic applications in neuroblastoma. J Hematol Oncol 2016; 9 (1): 100. doi: 10.1186/s13045-016-0334-6.

4. Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell 2006; 126 (5): 855–867. doi: 10.1016/j.cell.2006.08.019.

5. Munkley J, Elliott DJ. Hallmarks of glycosylation in cancer. Oncotarget 2016; 7 (23): 35478–35489. doi: 10.18632/oncotarget.8155.

6. Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer 2015; 15 (9): 540–555. doi: 10.1038/nrc3982.

7. Ladenson RP, Schwartz SO, Ivy AC. Incidence of the blood groups and the secretor factor in patients with pernicious anemia and stomach carcinoma. Am J Med Sci 1949; 217 (2): 194–197. doi: 10.1097/00000441-194902000-00011.

8. Dube DH, Bertozzi CR. Glycans in cancer and inflammation – potential for therapeutics and diagnostics. Nat Rev Drug Discov 2005; 4 (6): 477–488. doi: 10.1038/nrd1751.

9. Grishman E. Histochemical analysis of mucopolysaccharides occurring in mucus-producing tumors. Mixed tumors of the parotid gland, colloid carcinomas of the breast, and myxomas. Cancer 1952; 5 (4): 700–707. doi: 10.1002/1097-0142 (195207) 5: 4<700:: aid-cncr2820050408>3.0.co; 2-n.

10. Clerc F, Reiding KR, Jansen BC et al. Human plasma protein N-glycosylation. Glycoconj J 2016; 33 (3): 309–343. doi: 10.1007/s10719-015-9626-2.

11. Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 2005; 5 (11): 845–856. doi: 10.1038/nrc1739.

12. Demetriou M, Nabi IR, Coppolino M et al. Reduced contact-inhibition and substratum adhesion in epithelial cells expressing GlcNAc-transferase V. J Cell Biol 1995; 130 (2): 383–392. doi: 10.1083/jcb.130.2.383.

13. Zhao Y, Sato Y, Isaji T et al. Branched N-glycans regulate the biological functions of integrins and cadherins. FEBS J 2008; 275 (9): 1939–1948. doi: 10.1111/j.1742-4658.2008.06346.x.

14. Hernychová L, Uhrík L, Nenutil R et al. Glycoproteins in the sera of oncological patients. Klin Onkol 2019; 32 (Suppl 3): 39–45. doi: 10.14735/amko20193S.

15. Bereman MS, Williams TI, Muddiman DC. Development of a nanoLC LTQ orbitrap mass spectrometric method for profiling glycans derived from plasma from healthy, benign tumor control, and epithelial ovarian cancer patients. Anal Chem 2009; 81 (3): 1130–1136. doi: 10.1021/ac802262w.

16. Alley WR, Vasseur JA, Goetz JA et al. N-linked glycan structures and their expressions change in the blood sera of ovarian cancer patients. J Proteome Res 2012; 11 (4): 2282–2300. doi: 10.1021/pr201070k.

17. Abd Hamid UM, Royle L, Saldova R et al. A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression. Glycobiology 2008; 18 (12): 1105–1118. doi: 10.1093/glycob/cwn 095.

18. Kyselova Z, Mechref Y, Al Bataineh MM et al. Alterations in the serum glycome due to metastatic prostate cancer. J Proteome Res 2007; 6 (5): 1822–1832. doi: 10.1021/pr060664t.

19. Isailovic D, Kurulugama RT, Plasencia MD et al. Profiling of human serum glycans associated with liver cancer and cirrhosis by IMS-MS. J Proteome Res 2008; 7 (3): 1109–1117. doi: 10.1021/pr700702r.

20. Pierce A, Saldova R, Abd Hamid UM et al. Levels of specific glycans significantly distinguish lymph node-positive from lymph node-negative breast cancer patients. Glycobiology 2010; 20 (10): 1283–1288. doi: 10.1093/glycob/cwq090.

21. Saldova R, Haakensen VD, Rødland E et al. Serum N-glycome alterations in breast cancer during multimodal treatment and follow-up. Mol Oncol 2017; 11 (10): 1361–1379. doi: 10.1002/1878-0261.12105.

22. Gebrehiwot AG, Melka DS, Kassaye YM et al. Exploring serum and immunoglobulin G N-glycome as diag- nostic biomarkers for early detection of breast cancer in Ethiopian women. BMC Cancer 2019; 19 (1): 588. doi: 10.1186/s12885-019-5817-8.

23. Gebrehiwot AG, Melka DS, Kassaye YM et al. Healthy human serum N-glycan profiling reveals the influence of ethnic variation on the identified cancer-relevant glycan biomarkers. PLoS One 2018; 13 (12): e0209515. doi: 10.1371/journal.pone.0209515.

24. Ju L, Wang Y, Xie Q et al. Elevated level of serum glycoprotein bifucosylation and prognostic value in Chinese breast cancer. Glycobiology 2016; 26 (5): 460–471. doi: 10.1093/glycob/cwv117.

25. Lee SB, Bose S, Ahn SH et al. Breast cancer diagnosis by analysis of serum N-glycans using MALDI-TOF mass spectroscopy. PLoS One 2020; 15 (4): e0231004. doi: 10.1371/journal.pone.0231004.

26. Haakensen VD, Steinfeld I, Saldova R et al. Serum N-glycan analysis in breast cancer patients – relation to tumour biology and clinical outcome. Mol Oncol 2016; 10 (1): 59–72. doi: 10.1016/j.molonc.2015.08.002.

27. Murphy K, Murphy BT, Boyce S et al. Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer. Mol Oncol 2018; 12 (9): 1513–1525. doi: 10.1002/1878-0261.12348.

28. Gilgunn S, Murphy K, Stöckmann H et al. Glycosylation in indolent, significant and aggressive prostate cancer by automated high-throughput N-glycan profiling. Int J Mol Sci 2020; 21 (23): 9233. doi: 10.3390/ijms21239233.

29. Matsumoto T, Hatakeyama S, Yoneyama T et al. Serum N-glycan profiling is a potential biomarker for castration-resistant prostate cancer. Sci Rep 2019; 9 (1): 16761. doi: 10.1038/s41598-019-53384-y.

30. Zahradnikova M, Ihnatova I, Lattova E et al. N-Glycome changes reflecting resistance to platinum-based chemotherapy in ovarian cancer. J Proteom 2021; 230: 103964. doi: 10.1016/j.jprot.2020.103964.

31. Bartling B, Vanhooren V, Dewaele S et al. Altered desialylated plasma N-glycan profile in patients with non-small cell lung carcinoma. Cancer Biomark 2011; 10 (3–4): 145–154. doi: 10.3233/CBM-2012-0239.

32. Doherty M, Theodoratou E, Walsh I et al. Plasma N-glycans in colorectal cancer risk. Sci Rep 2018; 8 (1): 8655. doi: 10.1038/s41598-018-26805-7.

33. de Vroome SW, Holst S, Girondo MR et al. Serum N-glycome alterations in colorectal cancer associate with survival. Oncotarget 2018; 9 (55): 30610–30623. doi: 10.18632/oncotarget.25753.

34. Gaye MM, Valentine SJ, Hu Y et al. Ion mobility-mass spectrometry analysis of serum N-linked glycans from esophageal adenocarcinoma phenotypes. J Proteome Res 2012; 11 (12): 6102–6110. doi: 10.1021/pr300756e.

35. Lavine BK, White CG, Ding T et al. Wavelet based classification of MALDI-IMS-MS spectra of serum N-Linked glycans from normal controls and patients diagnosed with Barrett’s esophagus, high grade dysplasia, and esophageal adenocarcinoma. Chemom Intel Lab Syst 2018; 176: 74–81.

36. Gaye MM, Ding T, Shion H et al. Delineation of disease phenotypes associated with esophageal adenocarcinoma by MALDI-IMS-MS analysis of serum N-linked glycans. Analyst 2017; 142 (9): 1525–1535. doi: 10.1039/c6an02697d.

37. Zhang Z, Westhrin M, Bondt A et al. Serum protein N-glycosylation changes in multiple myeloma. Biochim Biophys Acta Gen Subj 2019; 1863 (5): 960–970. doi: 10.1016/j.bbagen.2019.03.001.

38. Vreeker GCM, Hanna-Sawires RG, Mohammed Y et al. Serum N-glycome analysis reveals pancreatic cancer disease signatures. Cancer Med 2020; 9 (22): 8519–8529. doi: 10.1002/cam4.3439.

39. Kawaguchi-Sakita N, Kaneshiro-Nakagawa K, Kawashima M et al. Serum immunoglobulin G Fc region N-glycosylation profiling by matrix-assisted laser desorption/ionization mass spectrometry can distinguish breast cancer patients from cancer-free controls. Biochem Biophys Res Commun 2016; 469 (4): 1140–1145. doi: 10.1016/j.bbrc.2015.12.114.

40. Zou X, Yao F, Yang F et al. Glycomic signatures of plasma igg improve preoperative prediction of the invasiveness of small lung nodules. Molecules 2020; 25 (1): 28. doi: 10.3390/molecules25010028.

41. Saldova R, Royle L, Radcliffe CM et al. Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG. Glycobiology 2007; 17 (12): 1344–1356. doi: 10.1093/glycob/cwm100.

42. Liu S, Cheng L, Fu Y et al. Characterization of IgG N-glycome profile in colorectal cancer progression by MALDI-TOF-MS. J Proteomics 2018; 181: 225–237. doi: 10.1016/j.jprot.2018.04.026.

43. Lee SH, Jeong S, Lee J et al. Glycomic profiling of targeted serum haptoglobin for gastric cancer using nano LC/MS and LC/MS/MS. Mol Biosyst 2016; 12 (12): 3611–3621. doi: 10.1039/c6mb00559d.

44. Balmaña M, Sarrats A, Llop E et al. Identification of potential pancreatic cancer serum markers: increased sialyl-Lewis X on ceruloplasmin. Clin Chim Acta 2015; 442: 56–62. doi: 10.1016/j.cca.2015.01.007.

45. Hülsmeier AJ, Paesold-Burda P, Hennet T. N-glycosylation site occupancy in serum glycoproteins using multiple reaction monitoring liquid chromatography-mass spectrometry. Mol Cell Proteomics 2007; 6 (12): 2132–2138. doi: 10.1074/mcp.M700361-MCP200.

46. Mariño K, Bones J, Kattla JJ et al. A systematic approach to protein glycosylation analysis: a path through the maze. Nat Chem Biol 2010; 6 (10): 713–723. doi: 10.1038/nchembio.437.

47. Hong Q, Ruhaak LR, Stroble C et al. A method for comprehensive flycosite-mapping and direct quantitation of serum glycoproteins. J Proteome Res 2015; 14 (12): 5179–5192. doi: 10.1021/acs.jproteome.5b00756.

48. Ueda K, Takami S, Saichi N et al. Development of serum glycoproteomic profiling technique; simultaneous identification of glycosylation sites and site-specific quantification of glycan structure changes. Mol Cell Proteomics 2010; 9 (9): 1819–1828. doi: 10.1074/mcp.2010/000893.

49. Liu L, Zhu B, Fang Z et al. Automated intact glycopeptide enrichment method facilitating highly reproducible analysis of serum site-specific N-glycoproteome. Anal Chem 2021; 93 (20): 7473–7480. doi: 10.1021/acs.analchem.1c00645.

50. Li Q, Kailemia MJ, Merleev AA et al. Site-specific glycosylation quantitation of 50 serum glycoproteins enhanced by predictive glycopeptidomics for improved disease biomarker discovery. Anal Chem 2019; 91 (8): 5433–5445. doi: 10.1021/acs.analchem.9b00776.

51. Takakura D, Harazono A, Hashii N et al. Selective glycopeptide profiling by acetone enrichment and LC/MS. J Proteomics 2014; 101: 17–30. doi: 10.1016/j.jprot.2014.02.005.

52. Mikami M, Tanabe K, Matsuo K et al. Fully-sialylated alpha-chain of complement 4-binding protein: diagnostic utility for ovarian clear cell carcinoma. Gynecol Oncol 2015; 139 (3): 520–528. doi: 10.1016/j.ygyno.2015.10. 012.

53. Tanabe K, Ikeda M, Hayashi M et al. Comprehensive serum glycopeptide spectra analysis combined with artificial intelligence (CSGSA-AI) to diagnose early-stage ovarian cancer. Cancers 2020; 12 (9): 2373. doi: 10.3390/cancers12092373.

54. Matsuo K, Tanabe K, Hayashi M et al. Utility of comprehensive serum glycopeptide spectra analysis (CSGSA) for the detection of early stage epithelial ovarian cancer. Cancers 2020; 12 (9): 2374. doi: 10.3390/cancers12092374.

55. Shinozaki E, Tanabe K, Akiyoshi T et al. Serum leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan: a novel colorectal cancer marker. BMC Cancer 2018; 18 (1): 406. doi: 10.1186/s12885-018-42 52-6.

56. Dobryszycka W. Biological functions of haptoglobin – new pieces to an old puzzle. Clin Chem Lab Med 1997; 35 (9): 647–654.

57. Sanda M, Pompach P, Brnakova Z et al. Quantitative liquid chromatography-mass spectrometry-multiple reaction monitoring (LC-MS-MRM) analysis of site-specific glycoforms of haptoglobin in liver disease. Mol Cell Proteomics 2013; 12 (5): 1294–1305. doi: 10.1074/mcp.M112.023325.

58. Pompach P, Brnakova Z, Sanda M et al. Site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma. Mol Cell Proteomics 2013; 12 (5): 1281–1293. doi: 10.1074/mcp.M112.023259.

59. Takahashi S, Sugiyama T, Shimomura M et al. Site--specific and linkage analyses of fucosylated N-glycans on haptoglobin in sera of patients with various types of cancer: possible implication for the differential diagnosis of cancer. Glycoconj J 2016; 33 (3): 471–482. doi: 10.1007/s10719-016-9653-7.

60. Ruhaak LR, Kim K, Stroble C et al. Protein-specific differential glycosylation of immunoglobulins in serum of ovarian cancer patients. J Proteome Res 2016; 15 (3): 1002–1010. doi: 10.1021/acs.jproteome.5b01 071.

61. Raman R, Raguram S, Venkataraman G et al. Glycomics: an integrated systems approach to structure-function relationships of glycans. Nat Methods 2005; 2 (11): 817–824. doi: 10.1038/nmeth807.

62. Cao L, Qu Y, Zhang Z et al. Intact glycopeptide characterization using mass spectrometry. Expert Rev Proteomics 2016; 13 (5): 513–522. doi: 10.1586/14789 450.2016.1172965.

63. Guerrini M, Raman R, Venkataraman G et al. A novel computational approach to integrate NMR spectroscopy and capillary electrophoresis for structure assignment of heparin and heparan sulfate oligosaccharides. Glycobiology 2002; 12 (11): 713–719. doi: 10.1093/glycob/ cwf084.

64. Pabst M, Altmann F. Glycan analysis by modern instrumental methods. Proteomics 2011; 11 (4): 631–643. doi: 10.1002/pmic.201000517.

65. Azadi P, Heiss C. Mass spectrometry of N-linked glycans. Methods Mol Biol 2009; 534: 37–51. doi: 10.1007/978-1-59745-022-5_3.

66. Harvey DJ. Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates. Mass Spectrom Rev 1999; 18 (6): 349–450. doi: 10.1002/ (SICI) 1098-2787 (1999) 18: 6<349:: AID-MAS1>3.0.CO; 2-H.

67. Alley WR, Mann BF, Novotny MV. High-sensitivity analytical approaches for the structural characterization of glycoproteins. Chem Rev 2013; 113 (4): 2668–2732. doi: 10.1021/cr3003714.

68. Dedvisitsakul P, Jacobsen S, Svensson B et al. Glycopeptide enrichment using a combination of ZIC-HILIC and cotton wool for exploring the glycoproteome of wheat flour albumins. J Proteome Res 2014; 13 (5): 2696–2703. doi: 10.1021/pr401282r.

69. Ruiz-May E, Catalá C, Rose JKC. N-glycoprotein enrichment by lectin affinity chromatography. Methods Mol Biol 2014; 1072: 633–643. doi: 10.1007/978-1-62703-631-3_43.

70. Zhang H, Li X-J, Martin DB et al. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechol 2003; 21 (6): 660–666. doi: 10.1038/nbt827.

71. Liu T, Qian WJ, Gritsenko MA et al. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res 2005; 4 (6): 2070–2080. doi: 10.1021/pr0502065.

72. Scott NE, Parker BL, Connolly AM et al. Simultaneous glycan-peptide characterization using hydrophilic interaction chromatography and parallel fragmentation by CID, higher energy collisional dissociation, and electron transfer dissociation MS applied to the N-linked glycoproteome of Campylobacter jejuni. Mol Cell Proteomics 2011; 10 (2): M000031–MCP201. doi: 10.1074/mcp.M000031-MCP201.

73. Bern M, Kil YJ, Becker C. Byonic: advanced peptide and protein identification software. Curr Protoc Bioinformatics 2012; 13: 13.20. doi: 10.1002/0471250953.bi1320s40.

74. Amon R, Rosenfeld R, Perlmutter S et al. Directed evolution of therapeutic antibodies targeting glycosylation in cancer. Cancers 2020; 12 (10): 2824. doi: 10.3390/cancers12102824.

75. Rabu C, McIntosh R, Jurasova Z et al. Glycans as targets for therapeutic antitumor antibodies. Future Oncol 2012; 8 (8): 943–960. doi: 10.2217/fon.12.88.

76. Gao Y, Luan X, Melamed J et al. Role of glycans on key cell surface receptors that regulate cell proliferation and cell death. Cells 2021; 10 (5): 1252. doi: 10.3390/cells10051252.