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Recognition of urinary N-linked glycopeptides in kidney cancer patients by hydrophilic carbohydrate functionalized magnetic metal organic framework combined with LC-MS/MS

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Abstract

A hydrophilic carbohydrate functionalized magnetic metal organic framework (Mag Zr-MOF@G6P) was synthesized via a facile one-step modification strategy for selective glycopeptide capture in virtue of hydrophilic interaction chromatography technique. The inherently hydrophilic Zr-MOF layer not only provides selective size-sieving pore structures but also offers large specific surface area to afford abundant affinity sites. Hydroxyl-rich glucose-6-phosphate was immobilized onto the Zr-MOF via a straightforward coordination manner to regulate its surface property, for the purpose of enhancing its hydrophilicity. Benefitting from the merits of Zr-MOF and glucose-6-phosphate, the as-designed composite exhibits good selectivity (the mass ratio of HRP digests to BSA digests was up to1:200) and low limit of detection (0.1 fmol μL−1) towards the recognition of glycopeptides from standard samples. More excitingly, glycopeptides in urine of healthy people and patients with kidney cancer were successfully enriched and identified by the combined liquid chromatography-mass spectrometry/mass spectrometry technology (LC-MS/MS). Further gene ontology analysis of molecular function and biological process revealed that 13 original glycoproteins of the identified glycopeptides from urine of patients significantly participate in diverse cancer-associated events, including collagen binding, immunoglobulin receptor binding, antigen binding, and complement activation process.

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References

  1. Lundberg E, Borner GHH (2019) Spatial proteomics: a powerful discovery tool for cell biology. Nat Rev Mol Cell Biol 20(5):285–302. https://doi.org/10.1038/s41580-018-0094-y

    Article  CAS  PubMed  Google Scholar 

  2. Christiansen MN, Chik J, Lee L, Anugraham M, Abrahams JL, Packer NH (2014) Cell surface protein glycosylation in cancer. Proteomics 14(4–5):525–546. https://doi.org/10.1002/pmic.201300387

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Hu X, Liu Q, Wu Y, Deng Z, Long J, Deng C (2019) Magnetic metal-organic frameworks containing abundant carboxylic groups for highly effective enrichment of glycopeptides in breast cancer serum. Talanta 204:446–454. https://doi.org/10.1016/j.talanta.2019.06.037

    Article  CAS  PubMed  Google Scholar 

  5. Kammeijer GSM, Nouta J, de la Rosette J, de Reijke TM, Wuhrer M (2018) An in-depth glycosylation assay for urinary prostate-specific antigen. Anal Chem 90(7):4414–4421. https://doi.org/10.1021/acs.analchem.7b04281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wu Y, Lin H, Xu Z, Li Y, Chen Z, Deng C (2020) Preparation of zwitterionic cysteine-modified silica microsphere capillary packed columns for the on-column enrichment and analysis of glycopeptides in human saliva. Anal Chim Acta 1096:1–8. https://doi.org/10.1016/j.aca.2019.11.032

    Article  CAS  PubMed  Google Scholar 

  7. Haj-Ahmad TA, Abdalla MA, Haj-Ahmad Y (2014) Potential urinary protein biomarker candidates for the accurate detection of prostate cancer among benign prostatic hyperplasia patients. J Cancer 5(2):103–114. https://doi.org/10.7150/jca.6890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gao Y (2015) Urine proteomics in kidney disease biomarker discovery. Springer Science+Business Media, London

    Book  Google Scholar 

  9. Sun N, Wu H, Shen X, Deng C (2019) Nanomaterials in proteomics. Adv Funct Mater 29(26):1900253. https://doi.org/10.1002/adfm.201900253

    Article  CAS  Google Scholar 

  10. Suttapitugsakul S, Sun F, Wu R (2020) Recent advances in glycoproteomic analysis by mass spectrometry. Anal Chem 92(1):267–291. https://doi.org/10.1021/acs.analchem.9b04651

    Article  CAS  PubMed  Google Scholar 

  11. Chen Z, Huang J, Li L (2019) Recent advances in mass spectrometry (MS)-based glycoproteomics in complex biological samples. Trends Analyt Chem 118:880–892. https://doi.org/10.1016/j.trac.2018.10.009

    Article  CAS  PubMed  Google Scholar 

  12. Sun N, Wang J, Yao J, Chen H, Deng C (2019) Magnetite nanoparticles coated with mercaptosuccinic acid-modified mesoporous titania as a hydrophilic sorbent for glycopeptides and phosphopeptides prior to their quantitation by LC-MS/MS. Mikrochim Acta 186(3):159. https://doi.org/10.1007/s00604-019-3274-3

    Article  CAS  PubMed  Google Scholar 

  13. Chu H, Hu X, Yao J, Yan G, Sun N, Deng C (2020) One-pot preparation of hydrophilic citric acid-magnetic nanoparticles for identification of glycopeptides in human saliva. Talanta 206:120178. https://doi.org/10.1016/j.talanta.2019.120178

    Article  CAS  PubMed  Google Scholar 

  14. Li Y, Sun N, Hu X, Li Y, Deng C (2019) Recent advances in nanoporous materials as sample preparation techniques for peptidome research. TrAC Trends Anal Chem 120:115658. https://doi.org/10.1016/j.trac.2019.115658

    Article  CAS  Google Scholar 

  15. Liu Q, Sun N, Deng C-h (2019) Recent advances in metal-organic frameworks for separation and enrichment in proteomics analysis. TrAC Trends Anal Chem 110:66–80. https://doi.org/10.1016/j.trac.2018.10.033

    Article  CAS  Google Scholar 

  16. Sun N, Wu H, Chen H, Shen X, Deng C (2019) Advances in hydrophilic nanomaterials for glycoproteomics. Chem Commun (Camb) 55(70):10359–10375. https://doi.org/10.1039/c9cc04124a

    Article  CAS  Google Scholar 

  17. Lu J, Luan J, Li Y, He X, Chen L, Zhang Y (1615) Hydrophilic maltose-modified magnetic metal-organic framework for highly efficient enrichment of N-linked glycopeptides. J Chromatogr A 2020:460754. https://doi.org/10.1016/j.chroma.2019.460754

    Article  CAS  Google Scholar 

  18. Liu Q, Deng CH, Sun N (2018) Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides. Nanoscale 10(25):12149–12155. https://doi.org/10.1039/c8nr03174f

    Article  CAS  PubMed  Google Scholar 

  19. Li J, Huan W, Xu K, Wang B, Zhang J, Zhu B, Wu M, Wang J (2020) Gold nanoparticle-glutathione-functionalized porous graphene oxide-based hydrophilic beads for the selective enrichment of N-linked glycopeptides. Mikrochim Acta 187(9):518. https://doi.org/10.1007/s00604-020-04519-w

    Article  CAS  PubMed  Google Scholar 

  20. Zheng H, Wang J, Gao M, Zhang X (2019) Titanium(IV)-functionalized zirconium-organic frameworks as dual-metal affinity probe for recognition of endogenous phosphopeptides prior to mass spectrometric quantification. Mikrochim Acta 186(12):829. https://doi.org/10.1007/s00604-019-3962-z

    Article  CAS  PubMed  Google Scholar 

  21. Garzon-Tovar L, Rodriguez-Hermida S, Imaz I, Maspoch D (2017) Spray drying for making covalent chemistry: postsynthetic modification of metal-organic frameworks. J Am Chem Soc 139(2):897–903. https://doi.org/10.1021/jacs.6b11240

    Article  CAS  PubMed  Google Scholar 

  22. Wang Z, Hu X, Sun N, Deng C (2019) Aptamer-functionalized magnetic metal organic framework as nanoprobe for biomarkers in human serum. Anal Chim Acta 1087:69–75. https://doi.org/10.1016/j.aca.2019.08.038

    Article  CAS  PubMed  Google Scholar 

  23. Arcuri C, Monarca L, Ragonese F, Mecca C, Bruscoli S, Giovagnoli S, Donato R, Bereshchenko O, Fioretti B, Costantino F (2018) Probing internalization effects and biocompatibility of ultrasmall zirconium metal-organic frameworks UiO-66 NP in U251 Glioblastoma Cancer cells. Nanomaterials 8(11). https://doi.org/10.3390/nano8110867

  24. Li Y, Wu H, Sun N, Deng C (2019) Fabrication of hydrophilic multilayer magnetic probe for salivary glycopeptidome analysis. J Chromatogr A 1587:24–33. https://doi.org/10.1016/j.chroma.2018.11.040

    Article  CAS  PubMed  Google Scholar 

  25. Ryu JH, Messersmith PB, Lee H (2018) Polydopamine surface chemistry: a decade of discovery. ACS Appl Mater Interfaces 10(9):7523–7540. https://doi.org/10.1021/acsami.7b19865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Katz MJ, Brown ZJ, Colon YJ, Siu PW, Scheidt KA, Snurr RQ, Hupp JT, Farha OK (2013) A facile synthesis of UiO-66, UiO-67 and their derivatives. Chem Commun (Camb) 49(82):9449–9451. https://doi.org/10.1039/c3cc46105j

    Article  CAS  Google Scholar 

  27. Yao J, Wang J, Sun N, Deng C (2017) One-step functionalization of magnetic nanoparticles with 4-mercaptophenylboronic acid for a highly efficient analysis of N-glycopeptides. Nanoscale 9(41):16024–16029. https://doi.org/10.1039/c7nr04206j

    Article  CAS  PubMed  Google Scholar 

  28. Wang J, Li J, Yan G, Gao M, Zhang X (2019) Preparation of a thickness-controlled mg-MOFs-based magnetic graphene composite as a novel hydrophilic matrix for the effective identification of the glycopeptide in the human urine. Nanoscale 11(8):3701–3709. https://doi.org/10.1039/c8nr10074h

    Article  CAS  PubMed  Google Scholar 

  29. Nam H, Kundu A, Brinkley GJ, Chandrashekar DS, Kirkman RL, Chakravarthi B, Orlandella RM, Norian LA, Sonpavde G, Ghatalia P, Fei F, Wei S, Varambally S, Sudarshan S (2020) PGC1alpha suppresses kidney cancer progression by inhibiting collagen-induced SNAIL expression. Matrix Biol 89:43–58. https://doi.org/10.1016/j.matbio.2020.01.001

    Article  CAS  PubMed  Google Scholar 

  30. Sirolli V, Pieroni L, Di Liberato L, Urbani A, Bonomini M (2019) Urinary peptidomic biomarkers in kidney diseases. Int J Mol Sci 21(1). https://doi.org/10.3390/ijms21010096

  31. Morais M, Dias F, Teixeira AL, Medeiros R (2020) Telomere length in renal cell carcinoma: the Jekyll and Hyde biomarker of ageing of the kidney. Cancer Manag Res 12:1669–1679. https://doi.org/10.2147/CMAR.S211225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hong Q, Wang S, Liu S, Chen X, Cai G (2020) LRG1 may accelerate the progression of ccRCC via the TGF-beta pathway. Biomed Res Int 2020:1285068–1285069. https://doi.org/10.1155/2020/1285068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Huang H (2018) Matrix Metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances. Sensors (Basel) 18(10). https://doi.org/10.3390/s18103249

  34. He XM, Liang XC, Chen X, Yuan BF, Zhou P, Zhang LN, Feng YQ (2017) High strength and hydrophilic chitosan microspheres for the selective enrichment of N-glycopeptides. Anal Chem 89(18):9712–9721. https://doi.org/10.1021/acs.analchem.7b01283

    Article  CAS  PubMed  Google Scholar 

  35. Peng J, Hu Y, Zhang H, Wan L, Wang L, Liang Z, Zhang L, Wu R (2019) High anti-interfering profiling of endogenous glycopeptides for human plasma by the dual-hydrophilic metal-organic framework. Anal Chem 91(7):4852–4859. https://doi.org/10.1021/acs.analchem.9b00542

    Article  CAS  PubMed  Google Scholar 

  36. Zunder SM, Gelderblom H, Tollenaar RA, Mesker WE (2020) The significance of stromal collagen organization in cancer tissue: an in-depth discussion of literature. Crit Rev Oncol Hematol 151:102907. https://doi.org/10.1016/j.critrevonc.2020.102907

    Article  PubMed  Google Scholar 

  37. Gadwa J, Karam SD (2020) Deciphering the intricate roles of radiation therapy and complement activation in cancer. Int J Radiat Oncol Biol Phys 108:46–55. https://doi.org/10.1016/j.ijrobp.2020.06.067

    Article  PubMed  Google Scholar 

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Funding

This work was financially supported by National Key R&D Program of China (2018YFA0507501) and the National Natural Science Foundation of China (21425518).

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Authors and Affiliations

  1. Department of Chemistry, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, 200433, Shanghai, China

    Xufang Hu, Yonglei Wu & Chunhui Deng

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  1. Xufang Hu
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Correspondence to Chunhui Deng.

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Hu, X., Wu, Y. & Deng, C. Recognition of urinary N-linked glycopeptides in kidney cancer patients by hydrophilic carbohydrate functionalized magnetic metal organic framework combined with LC-MS/MS. Microchim Acta 187, 616 (2020). https://doi.org/10.1007/s00604-020-04595-y

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