Skip to main content
SpringerLink
Log in

Discovery of Biomarkers Using Aptamers Evolved in Cell-SELEX Method

  • Chapter
  • First Online:
Aptamers Selected by Cell-SELEX for Theranostics

  • 1782 Accesses

Abstract

The knowledge of biomarkers relevant to diseases has a significant impact on the diagnosis, the prognosis, and the fundamental understanding of the disease. In the context of biomarker discovery in cell-SELEX, the definition of a biomarker referred to a molecular entity overly expressed in an immortalized cell line in which the origin of this cell is a diseased patient. This chapter focuses on an extensive discussion on how biomarkers can be discovered using aptamers evolved from cell-SELEX technology, with a particular emphasis on the systematic steps needs to follow to discover a biomarker. A comparison is made underlining current challenges of existing “omic”-based technologies of biomarker discovery. The utility of chemical versatility of aptamers in transforming aptamers evolved from cell-SELEX as a proteomic tool is discussed. Feasibility of post-proteomic target validation studies employing variety of biochemical techniques is highlighted with selected examples. The significant progress of aptamer-aided biomarker discovery is emphasized with six examples of aptamer-based biomarker discovery leading to the identification of novel marker or already established biomarker molecules. Chapter concludes with a discussion on current challenges that hinders the success of the field of aptamer-based biomarker discovery, and a discussion with potential solutions that could accelerate the progress of the field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Strimbu K, Tavel JA (2010) What are biomarkers? Current opinion in HIV and AIDS 5(6):463–466. doi:10.1097/COH.0b013e32833ed177

    Article  Google Scholar 

  2. Henry NL, Hayes DF (2012) Cancer biomarkers. Molecular oncology 6(2):140–146. doi:10.1016/j.molonc.2012.01.010

    Article  CAS  Google Scholar 

  3. Frangogiannis NG (2012) Biomarkers: hopes and challenges in the path from discovery to clinical practice. Translational research : the journal of laboratory and clinical medicine 159(4):197–204. doi:10.1016/j.trsl.2012.01.023

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Etzioni R, Urban N, Ramsey S, McIntosh M, Schwartz S, Reid B, Radich J, Anderson G, Hartwell L (2003) The case for early detection. Nat Rev Cancer 3(4):243–252. doi:10.1038/nrc1041

    Article  CAS  Google Scholar 

  6. Lin K, Lipsitz R, Miller T, Janakiraman S, Force USPST (2008) Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med 149(3):192–199

    Article  Google Scholar 

  7. Health Quality O (2007) Screening mammography for women aged 40 to 49 years at average risk for breast cancer: an evidence-based analysis. Ontario health technology assessment series 7(1):1–32

    Google Scholar 

  8. Babuin L, Jaffe AS (2005) Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne 173 (10):1191-1202. doi:10.1503/cmaj/051291

    Google Scholar 

  9. Vasan RS (2006) Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 113(19):2335–2362. doi:10.1161/CIRCULATIONAHA.104.482570

    Article  Google Scholar 

  10. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250(4988):1684–1689

    Article  CAS  Google Scholar 

  11. Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56(1):265–271

    CAS  Google Scholar 

  12. Fang X, Tan W (2010) Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach. Acc Chem Res 43(1):48–57. doi:10.1021/ar900101s

    Article  CAS  Google Scholar 

  13. Tang Z, Parekh P, Turner P, Moyer RW, Tan W (2009) Generating aptamers for recognition of virus-infected cells. Clin Chem 55(4):813–822. doi:10.1373/clinchem.2008.113514

    Article  CAS  Google Scholar 

  14. Ilyin SE, Belkowski SM, Plata-Salaman CR (2004) Biomarker discovery and validation: technologies and integrative approaches. Trends Biotechnol 22(8):411–416. doi:10.1016/j.tibtech.2004.06.005

    Article  CAS  Google Scholar 

  15. Welsh JB, Zarrinkar PP, Sapinoso LM, Kern SG, Behling CA, Monk BJ, Lockhart DJ, Burger RA, Hampton GM (2001) Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. Proceedings of the National Academy of Sciences of the United States of America 98 (3):1176-1181. doi:10.1073/pnas.98.3.1176

    Google Scholar 

  16. Velculescu VE, Zhang L, Vogelstein B, Kinzler KW (1995) Serial analysis of gene expression. Science 270(5235):484–487

    Article  CAS  Google Scholar 

  17. Ewing B, Green P (2000) Analysis of expressed sequence tags indicates 35,000 human genes. Nat Genet 25(2):232–234. doi:10.1038/76115

    Article  CAS  Google Scholar 

  18. Brinkman BM (2004) Splice variants as cancer biomarkers. Clin Biochem 37(7):584–594. doi:10.1016/j.clinbiochem.2004.05.015

    Article  CAS  Google Scholar 

  19. Scott A, Ambannavar R, Jeong J, Liu ML, Cronin MT (2011) RT-PCR-based gene expression profiling for cancer biomarker discovery from fixed, paraffin-embedded tissues. Methods Mol Biol 724:239–257. doi:10.1007/978-1-61779-055-3_15

    Article  CAS  Google Scholar 

  20. Evans CW, Wilson DA, Mills GN (2001) Quantitative competitive (qc) RT-PCR as a tool in biomarker analysis. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 6(1):7–14. doi:10.1080/135475001452733

    Article  CAS  Google Scholar 

  21. Stenvinkel P, Karimi M, Johansson S, Axelsson J, Suliman M, Lindholm B, Heimburger O, Barany P, Alvestrand A, Nordfors L, Qureshi AR, Ekstrom TJ, Schalling M (2007) Impact of inflammation on epigenetic DNA methylation - a novel risk factor for cardiovascular disease? J Intern Med 261(5):488–499. doi:10.1111/j.1365-2796.2007.01777.x

    Article  CAS  Google Scholar 

  22. Gorg A, Obermaier C, Boguth G, Harder A, Scheibe B, Wildgruber R, Weiss W (2000) The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21(6):1037–1053. doi:10.1002/(SICI)1522-2683(20000401)21:6<1037:AID-ELPS1037>3.0.CO;2-V

    Article  CAS  Google Scholar 

  23. Wulfkuhle JD, Liotta LA, Petricoin EF (2003) Proteomic applications for the early detection of cancer. Nat Rev Cancer 3(4):267–275. doi:10.1038/nrc1043

    Article  CAS  Google Scholar 

  24. Tannu NS, Hemby SE (2006) Two-dimensional fluorescence difference gel electrophoresis for comparative proteomics profiling. Nat Protoc 1(4):1732–1742. doi:10.1038/nprot.2006.256

    Article  CAS  Google Scholar 

  25. Jain KK (2010) The handbook of biomarkers. Springer, New York

    Book  Google Scholar 

  26. Rifai N, Gillette MA, Carr SA (2006) Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 24(8):971–983. doi:10.1038/nbt1235

    Article  CAS  Google Scholar 

  27. Reyzer ML, Caprioli RM (2005) MALDI mass spectrometry for direct tissue analysis: a new tool for biomarker discovery. J Proteome Res 4(4):1138–1142. doi:10.1021/pr050095+

    Article  CAS  Google Scholar 

  28. Issaq HJ, Veenstra TD, Conrads TP, Felschow D (2002) The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification. Biochemical and biophysical research communications 292(3):587–592. doi:10.1006/bbrc.2002.6678

    Article  CAS  Google Scholar 

  29. Chaurand P, Sanders ME, Jensen RA, Caprioli RM (2004) Proteomics in diagnostic pathology: profiling and imaging proteins directly in tissue sections. Am J Pathol 165(4):1057–1068. doi:10.1016/S0002-9440(10)63367-6

    Article  CAS  Google Scholar 

  30. Paweletz CP, Trock B, Pennanen M, Tsangaris T, Magnant C, Liotta LA, Petricoin EF 3rd (2001) Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: potential for new biomarkers to aid in the diagnosis of breast cancer. Dis Markers 17(4):301–307

    Article  CAS  Google Scholar 

  31. Robosky LC, Robertson DG, Baker JD, Rane S, Reily MD (2002) In vivo toxicity screening programs using metabonomics. Comb Chem High Throughput Screening 5(8):651–662

    Article  CAS  Google Scholar 

  32. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505–510

    Article  CAS  Google Scholar 

  33. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346(6287):818–822. doi:10.1038/346818a0

    Article  CAS  Google Scholar 

  34. Jayasena SD (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin Chem 45(9):1628–1650

    CAS  Google Scholar 

  35. Shangguan D, Li Y, Tang Z, Cao ZC, Chen HW, Mallikaratchy P, Sefah K, Yang CJ, Tan W (2006) Aptamers evolved from live cells as effective molecular probes for cancer study. Proceedings of the National Academy of Sciences of the United States of America 103 (32):11838-11843. doi:10.1073/pnas.0602615103

    Google Scholar 

  36. Sefah K, Tang ZW, Shangguan DH, Chen H, Lopez-Colon D, Li Y, Parekh P, Martin J, Meng L, Phillips JA, Kim YM, Tan WH (2009) Molecular recognition of acute myeloid leukemia using aptamers. Leukemia 23(2):235–244. doi:10.1038/leu.2008.335

    Article  CAS  Google Scholar 

  37. Tang Z, Shangguan D, Wang K, Shi H, Sefah K, Mallikratchy P, Chen HW, Li Y, Tan W (2007) Selection of aptamers for molecular recognition and characterization of cancer cells. Anal Chem 79(13):4900–4907. doi:10.1021/ac070189y

    Article  CAS  Google Scholar 

  38. Ballew JT, Murray JA, Collin P, Maki M, Kagnoff MF, Kaukinen K, Daugherty PS (2013) Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes. Proceedings of the National Academy of Sciences of the United States of America 110 (48):19330-19335. doi:10.1073/pnas.1314792110

    Google Scholar 

  39. Chang YM, Donovan MJ, Tan W (2013) Using aptamers for cancer biomarker discovery. Journal of nucleic acids 2013:817350. doi:10.1155/2013/817350

    Article  Google Scholar 

  40. Bunka DH, Stockley PG (2006) Aptamers come of age - at last. Nat Rev Microbiol 4(8):588–596. doi:10.1038/nrmicro1458

    Article  CAS  Google Scholar 

  41. Gold L, Ayers D, Bertino J, Bock C, Bock A, Brody EN, Carter J, Dalby AB, Eaton BE, Fitzwater T, Flather D, Forbes A, Foreman T, Fowler C, Gawande B, Goss M, Gunn M, Gupta S, Halladay D, Heil J, Heilig J, Hicke B, Husar G, Janjic N, Jarvis T, Jennings S, Katilius E, Keeney TR, Kim N, Koch TH, Kraemer S, Kroiss L, Le N, Levine D, Lindsey W, Lollo B, Mayfield W, Mehan M, Mehler R, Nelson SK, Nelson M, Nieuwlandt D, Nikrad M, Ochsner U, Ostroff RM, Otis M, Parker T, Pietrasiewicz S, Resnicow DI, Rohloff J, Sanders G, Sattin S, Schneider D, Singer B, Stanton M, Sterkel A, Stewart A, Stratford S, Vaught JD, Vrkljan M, Walker JJ, Watrobka M, Waugh S, Weiss A, Wilcox SK, Wolfson A, Wolk SK, Zhang C, Zichi D (2010) Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS ONE 5(12):e15004. doi:10.1371/journal.pone.0015004

    Article  CAS  Google Scholar 

  42. Mallikaratchy P, Tang Z, Kwame S, Meng L, Shangguan D, Tan W (2007) Aptamer directly evolved from live cells recognizes membrane bound immunoglobin heavy mu chain in Burkitt’s lymphoma cells. Molecular & cellular proteomics : MCP 6(12):2230–2238. doi:10.1074/mcp.M700026-MCP200

    Article  CAS  Google Scholar 

  43. Van Simaeys D, Turek D, Champanhac C, Vaizer J, Sefah K, Zhen J, Sutphen R, Tan W (2014) Identification of cell membrane protein stress-induced phosphoprotein 1 as a potential ovarian cancer biomarker using aptamers selected by cell systematic evolution of ligands by exponential enrichment. Anal Chem 86(9):4521–4527. doi:10.1021/ac500466x

    Article  Google Scholar 

  44. Shangguan D, Cao Z, Meng L, Mallikaratchy P, Sefah K, Wang H, Li Y, Tan W (2008) Cell-specific aptamer probes for membrane protein elucidation in cancer cells. J Proteome Res 7(5):2133–2139. doi:10.1021/pr700894d

    Article  CAS  Google Scholar 

  45. Yang M, Jiang G, Li W, Qiu K, Zhang M, Carter CM, Al-Quran SZ, Li Y (2014) Developing aptamer probes for acute myelogenous leukemia detection and surface protein biomarker discovery. Journal of hematology & oncology 7(1):5. doi:10.1186/1756-8722-7-5

    Article  CAS  Google Scholar 

  46. Ara MN, Hyodo M, Ohga N, Akiyama K, Hida K, Hida Y, Shinohara N, Harashima H (2014) Identification and expression of troponin T, a new marker on the surface of cultured tumor endothelial cells by aptamer ligand. Cancer medicine 3(4):825–834. doi:10.1002/cam4.260

    Article  CAS  Google Scholar 

  47. Parekh P, Tang Z, Turner PC, Moyer RW, Tan W (2010) Aptamers recognizing glycosylated hemagglutinin expressed on the surface of vaccinia virus-infected cells. Anal Chem 82(20):8642–8649. doi:10.1021/ac101801j

    Article  CAS  Google Scholar 

  48. Tan W, Donovan MJ, Jiang J (2013) Aptamers from cell-based selection for bioanalytical applications. Chem Rev 113(4):2842–2862. doi:10.1021/cr300468w

    Article  CAS  Google Scholar 

  49. Shangguan D, Cao ZC, Li Y, Tan W (2007) Aptamers evolved from cultured cancer cells reveal molecular differences of cancer cells in patient samples. Clin Chem 53(6):1153–1155. doi:10.1373/clinchem.2006.083246

    Article  CAS  Google Scholar 

  50. Xiao Z, Shangguan D, Cao Z, Fang X, Tan W (2008) Cell-specific internalization study of an aptamer from whole cell selection. Chemistry 14(6):1769–1775. doi:10.1002/chem.200701330

    Article  CAS  Google Scholar 

  51. Easty DJ, Mitchell PJ, Patel K, Florenes VA, Spritz RA, Bennett DC (1997) Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma. International journal of cancer Journal international du cancer 71(6):1061–1065

    Article  CAS  Google Scholar 

  52. Cambier JC, Campbell KS (1992) Membrane immunoglobulin and its accomplices: new lessons from an old receptor. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6(13):3207–3217

    CAS  Google Scholar 

  53. Adams MM, Rice AD, Moyer RW (2007) Rabbitpox virus and vaccinia virus infection of rabbits as a model for human smallpox. J Virol 81(20):11084–11095. doi:10.1128/JVI.00423-07

    Article  CAS  Google Scholar 

  54. Shida H, Dales S (1981) Biogenesis of vaccinia: carbohydrate of the hemagglutinin molecules. Virology 111(1):56–72

    Article  CAS  Google Scholar 

  55. Van Simaeys D, Lopez-Colon D, Sefah K, Sutphen R, Jimenez E, Tan W (2010) Study of the molecular recognition of aptamers selected through ovarian cancer cell-SELEX. PLoS ONE 5(11):e13770. doi:10.1371/journal.pone.0013770

    Article  Google Scholar 

  56. Walsh N, Larkin A, Swan N, Conlon K, Dowling P, McDermott R, Clynes M (2011) RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation. Cancer Lett 306(2):180–189. doi:10.1016/j.canlet.2011.03.004

    Article  CAS  Google Scholar 

  57. Wang TH, Chao A, Tsai CL, Chang CL, Chen SH, Lee YS, Chen JK, Lin YJ, Chang PY, Wang CJ, Chao AS, Chang SD, Chang TC, Lai CH, Wang HS (2010) Stress-induced phosphoprotein 1 as a secreted biomarker for human ovarian cancer promotes cancer cell proliferation. Molecular & cellular proteomics : MCP 9(9):1873–1884. doi:10.1074/mcp.M110.000802

    Article  CAS  Google Scholar 

  58. Ara MN, Hyodo M, Ohga N, Hida K, Harashima H (2012) Development of a novel DNA aptamer ligand targeting to primary cultured tumor endothelial cells by a cell-based SELEX method. PLoS ONE 7(12):e50174. doi:10.1371/journal.pone.0050174

    Article  CAS  Google Scholar 

  59. Ara MN, Matsuda T, Hyodo M, Sakurai Y, Hatakeyama H, Ohga N, Hida K, Harashima H (2014) An aptamer ligand based liposomal nanocarrier system that targets tumor endothelial cells. Biomaterials 35(25):7110–7120. doi:10.1016/j.biomaterials.2014.04.087

    Article  CAS  Google Scholar 

  60. Risnik VV, Verin AD, Gusev NB (1985) Comparison of the structure of two cardiac troponin T isoforms. Biochem J 225(2):549–552

    CAS  Google Scholar 

  61. Virgo P, Denning-Kendall PA, Erickson-Miller CL, Singha S, Evely R, Hows JM, Freeman SD (2003) Identification of the CD33-related Siglec receptor, Siglec-5 (CD170), as a useful marker in both normal myelopoiesis and acute myeloid leukaemias. Br J Haematol 123(3):420–430

    Article  Google Scholar 

  62. Mayer G, Ahmed MS, Dolf A, Endl E, Knolle PA, Famulok M (2010) Fluorescence-activated cell sorting for aptamer SELEX with cell mixtures. Nat Protoc 5(12):1993–2004. doi:10.1038/nprot.2010.163

    Article  CAS  Google Scholar 

  63. Yang L, Zhang X, Ye M, Jiang J, Yang R, Fu T, Chen Y, Wang K, Liu C, Tan W (2011) Aptamer-conjugated nanomaterials and their applications. Adv Drug Deliv Rev 63(14–15):1361–1370. doi:10.1016/j.addr.2011.10.002

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Lehman College-City University of New York, New Science Hall-Office S-4404/Lab S-4401, 250 Bedford Park Blvd. West, Bronx, NY, 10468, USA

    Prabodhika Mallikaratchy, Hasan Zumrut & Naznin Ara

Authors
  1. Prabodhika Mallikaratchy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hasan Zumrut
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naznin Ara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Prabodhika Mallikaratchy .

Editor information

Editors and Affiliations

  1. Department of Chemistry, Hunan University, Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering, Changsha, China & University of Florida, Gainesville, Florida, USA

    Weihong Tan

  2. Institute of Chemistry, Chinese Academy of Sciences, Beijing, China

    Xiaohong Fang

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Mallikaratchy, P., Zumrut, H., Ara, N. (2015). Discovery of Biomarkers Using Aptamers Evolved in Cell-SELEX Method. In: Tan, W., Fang, X. (eds) Aptamers Selected by Cell-SELEX for Theranostics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46226-3_12

Download citation

Publish with us

Policies and ethics

Search

Navigation