Advertisement

Analytical and Bioanalytical Chemistry

, Volume 410, Issue 8, pp 2059–2065 | Cite as

Post-translational modifications in tumor biomarkers: the next challenge for aptamers?

  • Ana Díaz-Fernández
  • Rebeca Miranda-Castro
  • Noemí de-los-Santos-Álvarez
  • María Jesús Lobo-CastañónEmail author
Feature Article

Abstract

Advances in proteomics have fueled the search for novel cancer biomarkers with higher selectivity. Differential expression of low abundant proteins has been the usual way of finding those biomarkers. The existence of a selective receptor for each biomarker is compulsory for their use in diagnostic/prognostic assays. Antibodies are the receptors of choice in most cases although aptamers are becoming familiar because of their facile and reproducible synthesis, chemical stability as well as comparable affinity and selectivity. In recent years, it has been reported that the pattern of post-translational modifications, altered under neoplastic disease, is a better predictive biomarker than the total protein level. Among others, abnormal glycosylation is attracting great attention. Lectins and antibodies are being used for identification and detection of the carbohydrate moiety with low level of discrimination among various glycoproteins. Such level of selectivity is critical to bring next-generation biomarkers to the clinic. Aptamers that can be rationally tailored for a certain molecule domain can become the golden receptor to specifically detect aberrant glycosylation at each protein or even at each glycosylation site, providing new diagnostic tools for early detection of cancer.

Graphical abstract

Aptamers may specifically differentiate normal from aberrant glycoproteins

Keywords

Aptamers Cancer diagnostics Glycans Tumor biomarkers 

Notes

Acknowledgments

The authors acknowledge the support provided by the Spanish Ministerio de Economía y Competitividad (Project No. CTQ2015-63567-R), and the Principado de Asturias government (Project FC15-GRUPIN14-025, co-financed by FEDER funds).

Compliance with ethical standards

Conflict of interest

The authors declare that they have not conflict of interest.

References

  1. 1.
    Glavey SV, Huynh D, Reagan MR, Manier S, Moschetta M, Kawano Y, et al. The cancer glycome: carbohydrates as mediators of metastasis. Blood Rev. 2015;29(4):269–79.Google Scholar
  2. 2.
    Palecek E, Tkac J, Bartosik M, Bertok T, Ostatna V, Palecek J. Electrochemistry of nonconjugated proteins and glycoproteins. Toward sensors for biomedicine and glycomics. Chem Rev. 2015;115(5):2045–108.CrossRefGoogle Scholar
  3. 3.
    Miyoshi E, Moriwaki K, Terao N, Tan CC, Terao M, Nakagawa T, et al. Fucosylation is a promising target for cancer diagnosis and therapy. Biomol Ther. 2012;2(1):34–45.Google Scholar
  4. 4.
    Vajaria BN, Patel PS. Glycosylation: a hallmark of cancer? Glycoconj J. 2017;34(2):147–56.CrossRefGoogle Scholar
  5. 5.
    Munkley J, Elliott DJ. Hallmarks of glycosylation in cancer. Oncotarget. 2016;7(23):35478–89.CrossRefGoogle Scholar
  6. 6.
    Shajahan A, Heiss C, Ishihara M, Azadi P. Glycomic and glycoproteomic analysis of glycoproteins—a tutorial. Anal Bioanal Chem. 2017;409(19):4483–505.CrossRefGoogle Scholar
  7. 7.
    Jin S, Cheng YF, Reid S, Li MY, Wang BH. Carbohydrate recognition by boronolectins, small molecules, and lectins. Med Res Rev. 2010;30(2):171–257.Google Scholar
  8. 8.
    Stowell SR, Ju T, Cummings RD. Protein glycosylation in cancer. Annu Rev Pathol. 2015;10:473–510.CrossRefGoogle Scholar
  9. 9.
    Hong X, Ma MZ, Gildersleeve JC, Chowdhury S, Barchi JJ Jr, Mariuzza RA, et al. Sugar-binding proteins from fish: selection of high affinity “Lambodies” that recognize biomedically relevant glycans. ACS Chem Biol. 2013;8(1):152–60.Google Scholar
  10. 10.
    Tan ZJ, Yin HD, Nie S, Lin ZX, Zhu JH, Ruffin MT, et al. Large-scale identification of core-fucosylated glycopeptide sites in pancreatic cancer serum using mass spectrometry. J Proteome Res. 2015;14(4):1968–78.Google Scholar
  11. 11.
    Zhou J, Yang W, Hu Y, Hoti N, Liu Y, Shah P, et al. Site-specific fucosylation analysis identifying glycoproteins associated with aggressive prostate cancer cell lines using tandem affinity enrichments of intact glycopeptides followed by mass spectrometry. Anal Chem. 2017;89(14):7623–30.Google Scholar
  12. 12.
    Belicky S, Katrlik J, Tkac J. Glycan and lectin biosensors. Essays Biochem. 2016;60(1):37–47.CrossRefGoogle Scholar
  13. 13.
    Sun W, Du L, Li M. Aptamer-based carbohydrate recognition. Curr Pharm Des. 2010;16(20):2269–78.CrossRefGoogle Scholar
  14. 14.
    Dunn MR, Jimenez RM, Chaput JC. Analysis of aptamer discovery and technology. Nat Rev Chem. 2017;1:0076.  https://doi.org/10.1038/s41570-017-0076.CrossRefGoogle Scholar
  15. 15.
    de-los- Santos-Álvarez N, Lobo-Castañón MJ, Miranda-Ordieres AJ, Tuñón-Blanco P. Modified-RNA aptamer-based sensor for competitive impedimetric assay of neomycin B. J Am Chem Soc. 2007;129(13):3808–9.CrossRefGoogle Scholar
  16. 16.
    Zhang J, Loo RRO, Loo JA. Structural characterization of a thrombin-aptamer complex by high resolution native top-down mass spectrometry. J Am Soc Mass Spectrom. 2017;28(9):1815–22.CrossRefGoogle Scholar
  17. 17.
    Liu Y, Kuan CT, Mi J, Zhang X, Clary BM, Bigner DD, et al. Aptamers selected against the unglycosylated EGFRvIII ectodomain and delivered intracellularly reduce membrane-bound EGFRvIII and induce apoptosis. Biol Chem. 2009;390(2):137–44.Google Scholar
  18. 18.
    Ray P, Sullenger BA, White RR. Further characterization of the target of a potential aptamer biomarker for pancreatic cancer: cyclophilin B and its posttranslational modifications. Nucleic Acid Ther. 2013;23(6):435–42.CrossRefGoogle Scholar
  19. 19.
    Jeong S, Eom T, Kim S, Lee S, Yu J. In vitro selection of the RNA aptamer against the Sialyl Lewis X and its inhibition of the cell adhesion. Biochem Biophys Res Commun. 2001;281(1):237–43.CrossRefGoogle Scholar
  20. 20.
    Cho S, Lee BR, Cho BK, Kim JH, Kim BG. In vitro selection of sialic acid specific RNA aptamer and its application to the rapid sensing of sialic acid modified sugars. Biotechnol Bioeng. 2013;110(3):905–13.CrossRefGoogle Scholar
  21. 21.
    Gong S, Ren HL, Tian RY, Lin C, Hu P, Li YS, et al. A novel analytical probe binding to a potential carcinogenic factor of N-glycolylneuraminic acid by SELEX. Biosens Bioelectron. 2013;49:547–54.Google Scholar
  22. 22.
    Li MY, Lin N, Huang Z, Du LP, Altier C, Fang H, et al. Selecting aptamers for a glycoprotein through the incorporation of the boronic acid moiety. J Am Chem Soc. 2008;130(38):12636–8.Google Scholar
  23. 23.
    Lao YH, Chiang HY, Yang DK, Peck K, Chen LC. Selection of aptamers targeting the sialic acid receptor of hemagglutinin by epitope-specific SELEX. Chem Commun. 2014;50(63):8719–22.CrossRefGoogle Scholar
  24. 24.
    Ferreira CS, Cheung MC, Missailidis S, Bisland S, Gariepy J. Phototoxic aptamers selectively enter and kill epithelial cancer cells. Nucleic Acids Res. 2009;37(3):866–76.CrossRefGoogle Scholar
  25. 25.
    Rose CM, Hayes MJ, Stettler GR, Hickey SF, Axelrod TM, Giustini NP, et al. Capillary electrophoretic development of aptamers for a glycosylated VEGF peptide fragment. Analyst. 2010;135(11):2945–51.Google Scholar
  26. 26.
    Miyoshi E, Kamada Y. Application of glycoscience to the early detection of pancreatic cancer. Cancer Sci. 2016;107(10):1357–62.CrossRefGoogle Scholar
  27. 27.
    Kobayashi Y, Tateno H, Dohra H, Moriwaki K, Miyoshi E, Hirabayashi J, et al. A novel core fucose-specific lectin from the mushroom Pholiota squarrosa. J Biol Chem. 2012;287(41):33973–82.Google Scholar
  28. 28.
    Pfeiffer F, Rosenthal M, Siegl J, Ewers J, Mater G. Customised nucleic acid libraries for enhanced aptamer selection and performance. Curr Opin Biotechnol. 2017;48:11–8.CrossRefGoogle Scholar
  29. 29.
    Gold L, Ayers D, Bertino J, Bock C, Bock A, Brody EN, et al. Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS One. 2010;5:e15004.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Dpto. Química Física y AnalíticaUniversidad de OviedoOviedoSpain

Personalised recommendations