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Novel methodologies in analysis of small molecule biomarkers and living cells

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Tumor Biology

Abstract

Enzyme-linked immuno-sorbent assay (ELISA) is widely used for biomarker detection. A good biomarker can distinguish patients from healthy or benign diseases. However, the ELISA method is not suitable for small molecule or trace substance detection. Along with the development of new technologies, an increasing level of biomaterials, especially small molecules, will be identified as novel biomarkers. Quantitative immuno-PCR, chromatography–mass spectrometry, and nucleic acid aptamer are emerging methodologies for detection of small molecule biomarkers, even in living cells. In this review, we focus on these novel technologies and their potential for small molecule biomarkers and living cell analysis.

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References

  1. Wayner EA, Quek SI, Ahmad R, Ho ME, Loprieno MA, Zhou Y, et al. Development of an ELISA to detect the secreted prostate cancer biomarker AGR2 in voided urine. Prostate. 2012;72(9):1023–34. doi:10.1002/pros.21508.

    Article  CAS  PubMed  Google Scholar 

  2. Anborgh PH, Wilson SM, Tuck AB, Winquist E, Schmidt N, Hart R, et al. New dual monoclonal ELISA for measuring plasma osteopontin as a biomarker associated with survival in prostate cancer: clinical validation and comparison of multiple ELISAs. Clin Chem. 2009;55(5):895–903. doi:10.1373/clinchem.2008.117465.

    Article  CAS  PubMed  Google Scholar 

  3. Yousef GM, Polymeris ME, Grass L, Soosaipillai A, Chan PC, Scorilas A, et al. Human kallikrein 5: a potential novel serum biomarker for breast and ovarian cancer. Cancer Res. 2003;63(14):3958–65.

    CAS  PubMed  Google Scholar 

  4. Tahir SA, Ren C, Timme TL, Gdor Y, Hoogeveen R, Morrisett JD, et al. Development of an immunoassay for serum caveolin-1: a novel biomarker for prostate cancer. Clin cancer res : an off j of the Am Assoc for Cancer Res. 2003;9(10 Pt 1):3653–9.

    CAS  Google Scholar 

  5. Borgono CA, Grass L, Soosaipillai A, Yousef GM, Petraki CD, Howarth DH, et al. Human kallikrein 14: a new potential biomarker for ovarian and breast cancer. Cancer Res. 2003;63(24):9032–41.

    CAS  PubMed  Google Scholar 

  6. McDermed JE, Sanders R, Fait S, Klem RE, Sarno MJ, Adams TH, et al. Nucleic acid detection immunoassay for prostate-specific antigen based on immuno-PCR methodology. Clin Chem. 2012;58(4):732–40. doi:10.1373/clinchem.2011.170290.

    Article  CAS  PubMed  Google Scholar 

  7. Niemeyer CM, Adler M, Wacker R. Detecting antigens by quantitative immuno-PCR. Nat Protoc. 2007;2(8):1918–30. doi:10.1038/nprot.2007.267.

    Article  CAS  PubMed  Google Scholar 

  8. Suzuki A, Itoh F, Hinoda Y, Imai K. Double determinant immuno-polymerase chain reaction: a sensitive method for detecting circulating antigens in human sera. Jpn J Cancer Res. 1995;86(9):885–9.

    Article  CAS  PubMed  Google Scholar 

  9. Zhou H, Fisher RJ, Papas TS. Universal immuno-PCR for ultra-sensitive target protein detection. Nucleic Acids Res. 1993;21(25):6038–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sano T, Smith CL, Cantor CR. Immuno-PCR: very sensitive antigen detection by means of specific antibody-DNA conjugates. Science. 1992;258(5079):120–2.

    Article  CAS  PubMed  Google Scholar 

  11. Ye Q, Zhuang H, Zhou C. Detection of naphthalene by real-time immuno-PCR using molecular beacon. Mol Cell Probes. 2009;23(1):29–34. doi:10.1016/j.mcp.2008.10.004.

    Article  CAS  PubMed  Google Scholar 

  12. Chen HY, Zhuang HS. Real-time immuno-PCR assay for detecting PCBs in soil samples. Anal Bioanal Chem. 2009;394(4):1205–11. doi:10.1007/s00216-009-2787-8.

    Article  CAS  PubMed  Google Scholar 

  13. Deng MJ, Xiao XZ, Zhang YM, Wu XH, Zhu LH, Xin XQ, et al. A highly sensitive immuno-PCR assay for detection of H5N1 avian influenza virus. Mol Biol Rep. 2011;38(3):1941–8. doi:10.1007/s11033-010-0315-8.

    Article  CAS  PubMed  Google Scholar 

  14. Singer D, Soininen H, Alafuzoff I, Hoffmann R. Immuno-PCR-based quantification of multiple phosphorylated tau-epitopes linked to Alzheimer’s disease. Anal Bioanal Chem. 2009;395(7):2263–7. doi:10.1007/s00216-009-3208-8.

    Article  CAS  PubMed  Google Scholar 

  15. Ye G, Zhu B, Yao Z, Yin P, Lu X, Kong H, et al. Analysis of urinary metabolic signatures of early hepatocellular carcinoma recurrence after surgical removal using gas chromatography–mass spectrometry. J Proteome Res. 2012;11(8):4361–72. doi:10.1021/pr300502v.

    Article  CAS  PubMed  Google Scholar 

  16. Jentzmik F, Stephan C, Miller K, Schrader M, Erbersdobler A, Kristiansen G, et al. Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours. Eur Urol. 2010;58(1):12–8. doi:10.1016/j.eururo.2010.01.035. discussion 20–1.

    Article  CAS  PubMed  Google Scholar 

  17. Silva CL, Passos M, Camara JS. Investigation of urinary volatile organic metabolites as potential cancer biomarkers by solid-phase microextraction in combination with gas chromatography–mass spectrometry. Br J Cancer. 2011;105(12):1894–904. doi:10.1038/bjc.2011.437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lin L, Huang Z, Gao Y, Chen Y, Hang W, Xing J, et al. LC-MS-based serum metabolic profiling for genitourinary cancer classification and cancer type-specific biomarker discovery. Proteomics. 2012;12(14):2238–46. doi:10.1002/pmic.201200016.

    Article  CAS  PubMed  Google Scholar 

  19. Chen F, Xue J, Zhou L, Wu S, Chen Z. Identification of serum biomarkers of hepatocarcinoma through liquid chromatography/mass spectrometry-based metabonomic method. Anal Bioanal Chem. 2011;401(6):1899–904. doi:10.1007/s00216-011-5245-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Monteleone M, Naccarato A, Sindona G, Tagarelli A. A reliable and simple method for the assay of neuroendocrine tumor markers in human urine by solid-phase microextraction-gas chromatography-triple quadrupole mass spectrometry. Anal Chim Acta. 2013;759:66–73. doi:10.1016/j.aca.2012.11.017.

    Article  CAS  PubMed  Google Scholar 

  21. Falk RT, Brinton LA, Dorgan JF, Fuhrman BJ, Veenstra TD, Xu X, et al. Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case–control study. Breast Cancer Res. 2013;15(2):R34. doi:10.1186/bcr3416.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yang N, Feng S, Shedden K, Xie X, Liu Y, Rosser CJ, et al. Urinary glycoprotein biomarker discovery for bladder cancer detection using LC/MS-MS and label-free quantification. Clin Cancer Res. 2011;17(10):3349–59. doi:10.1158/1078-0432.CCR-10-3121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. de Castro J, Md, Rodriguez MC, Martinez-Zorzano VS, Sanchez-Rodriguez P, Sanchez-Yague J. Erythrocyte Fatty acids as potential biomarkers in the diagnosis of advanced lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer. Am J Clin Pathol. 2014;142(1):111–20. doi:10.1309/AJCP1QUQQLLT8BLI142/1/111 [pii].

  24. Arlt W, Biehl M, Taylor AE, Hahner S, Libe R, Hughes BA, et al. Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. J Clin Endocrinol Metab. 2011;96(12):3775–84. doi:10.1210/jc.2011-1565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yu L, Aa J, Xu J, Sun M, Qian S, Cheng L, et al. Metabolomic phenotype of gastric cancer and precancerous stages based on gas chromatography time-of-flight mass spectrometry. J Gastroenterol Hepatol. 2011;26(8):1290–7. doi:10.1111/j.1440-1746.2011.06724.x.

    Article  CAS  PubMed  Google Scholar 

  26. Lee SY, Park NH, Jeong EK, Wi JW, Kim CJ, Kim JY, et al. Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2012;900:1–10. doi:10.1016/j.jchromb.2012.05.011.

    Article  CAS  PubMed  Google Scholar 

  27. Ganti S, Taylor SL, Abu Aboud O, Yang J, Evans C, Osier MV, et al. Kidney tumor biomarkers revealed by simultaneous multiple matrix metabolomics analysis. Cancer Res. 2012;72(14):3471–9. doi:10.1158/0008-5472.CAN-11-3105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fuchs P, Loeseken C, Schubert JK, Miekisch W. Breath gas aldehydes as biomarkers of lung cancer. Int j of cancer J int du cancer. 2010;126(11):2663–70. doi:10.1002/ijc.24970.

    CAS  Google Scholar 

  29. Gao X, Pujos-Guillot E, Sebedio JL. Development of a quantitative metabolomic approach to study clinical human fecal water metabolome based on trimethylsilylation derivatization and GC/MS analysis. Anal Chem. 2010;82(15):6447–56. doi:10.1021/ac1006552.

    Article  CAS  PubMed  Google Scholar 

  30. Kapsimali DC, Zachariadis GA. Comparison of tetraethylborate and tetraphenylborate for selenite determination in human urine by gas chromatography mass spectrometry, after headspace solid phase microextraction. Talanta. 2010;80(3):1311–7. doi:10.1016/j.talanta.2009.09.022.

    Article  CAS  PubMed  Google Scholar 

  31. Chen M, Su M, Zhao L, Jiang J, Liu P, Cheng J, et al. Metabonomic study of aristolochic acid-induced nephrotoxicity in rats. J Proteome Res. 2006;5(4):995–1002. doi:10.1021/pr050404w.

    Article  CAS  PubMed  Google Scholar 

  32. Qiu Y, Su M, Liu Y, Chen M, Gu J, Zhang J, et al. Application of ethyl chloroformate derivatization for gas chromatography–mass spectrometry based metabonomic profiling. Anal Chim Acta. 2007;583(2):277–83. doi:10.1016/j.aca.2006.10.025.

    Article  CAS  PubMed  Google Scholar 

  33. Chen M, Ni Y, Duan H, Qiu Y, Guo C, Jiao Y, et al. Mass spectrometry-based metabolic profiling of rat urine associated with general toxicity induced by the multiglycoside of Tripterygium wilfordii Hook. f. Chem Res Toxicol. 2008;21(2):288–94. doi:10.1021/tx7002905.

    Article  CAS  PubMed  Google Scholar 

  34. Duru N, Fan M, Candas D, Menaa C, Liu HC, Nantajit D, et al. HER2-associated radioresistance of breast cancer stem cells isolated from HER2-negative breast cancer cells. Clin Cancer Res. 2012;18(24):6634–47. doi:10.1158/1078-0432.CCR-12-1436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Meyer TE, Fox SD, Issaq HJ, Xu X, Chu LW, Veenstra TD, et al. A reproducible and high-throughput HPLC/MS method to separate sarcosine from alpha- and beta-alanine and to quantify sarcosine in human serum and urine. Anal Chem. 2011;83(14):5735–40. doi:10.1021/ac201003r.

    Article  CAS  PubMed  Google Scholar 

  36. Hsu WY, Lin WD, Tsai Y, Lin CT, Wang HC, Jeng LB, et al. Analysis of urinary nucleosides as potential tumor markers in human breast cancer by high performance liquid chromatography/electrospray ionization tandem mass spectrometry. Clin Chim Acta. 2011;412(19–20):1861–6. doi:10.1016/j.cca.2011.06.027.

    Article  CAS  PubMed  Google Scholar 

  37. Baumann F, Regenthal R, Burgos-Guerrero IL, Hegerl U, Preiss R. Determination of nicotine and cotinine in human serum by means of LC/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878(1):107–11. doi:10.1016/j.jchromb.2009.11.032.

    Article  CAS  PubMed  Google Scholar 

  38. Kuribayashi R, Hashii N, Harazono A, Kawasaki N. Rapid evaluation for heterogeneities in monoclonal antibodies by liquid chromatography/mass spectrometry with a column-switching system. J Pharm Biomed Anal. 2012;67–68:1–9. doi:10.1016/j.jpba.2012.04.005.

    Article  PubMed  Google Scholar 

  39. Savolainen K, Kiimamaa R, Halonen T. High-throughput analysis of testosterone in serum samples by on-line solid phase extraction liquid chromatography-tandem mass spectrometry. Clin Chem Lab Med. 2011;49(11):1845–8. doi:10.1515/CCLM.2011.663.

    Article  CAS  PubMed  Google Scholar 

  40. Ferreiro-Vera C, Mata-Granados JM, Priego-Capote F, Quesada-Gomez JM, de Castro MD L. Automated targeting analysis of eicosanoid inflammation biomarkers in human serum and in the exometabolome of stem cells by SPE-LC-MS/MS. Anal Bioanal Chem. 2011;399(3):1093–103. doi:10.1007/s00216-010-4400-6.

    Article  CAS  PubMed  Google Scholar 

  41. Watanabe K, Ishikawa C, Kuwahara H, Sato K, Komuro S, Nakagawa T, et al. A new methodology for simultaneous quantification of total-Abeta, Abetax-38, Abetax-40, and Abetax-42 by column-switching LC/MS/MS. Anal Bioanal Chem. 2012;402(6):2033–42. doi:10.1007/s00216-011-5648-1.

    Article  CAS  PubMed  Google Scholar 

  42. Kennedy JH, Aurand C, Shirey R, Laughlin BC, Wiseman JM. Coupling desorption electrospray ionization with solid-phase microextraction for screening and quantitative analysis of drugs in urine. Anal Chem. 2010;82(17):7502–8. doi:10.1021/ac101295g.

    Article  CAS  PubMed  Google Scholar 

  43. Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990;346(6287):818–22. doi:10.1038/346818a0.

    Article  CAS  PubMed  Google Scholar 

  44. Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990;249(4968):505–10.

    Article  CAS  PubMed  Google Scholar 

  45. Wu J, Wang C, Li X, Song Y, Wang W, Li C, et al. Identification, characterization and application of a G-quadruplex structured DNA aptamer against cancer biomarker protein anterior gradient homolog 2. PLoS ONE. 2012;7(9):e46393. doi:10.1371/journal.pone.0046393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kiani Z, Shafiei M, Rahimi-Moghaddam P, Karkhane AA, Ebrahimi SA. In vitro selection and characterization of deoxyribonucleic acid aptamers for digoxin. Anal Chim Acta. 2012;748:67–72. doi:10.1016/j.aca.2012.08.025.

    Article  CAS  PubMed  Google Scholar 

  47. Mallikaratchy P, Stahelin RV, Cao Z, Cho W, Tan W. Selection of DNA ligands for protein kinase C-delta. Chem Commun (Camb). 2006 (30):3229–31. doi:10.1039/b604778e.

  48. Kunii T, Ogura S, Mie M, Kobatake E. Selection of DNA aptamers recognizing small cell lung cancer using living cell-SELEX. Analyst. 2011;136(7):1310–2. doi:10.1039/c0an00962h.

    Article  CAS  PubMed  Google Scholar 

  49. Zhang X, Zhang J, Ma Y, Pei X, Liu Q, Lu B, et al. A cell-based single-stranded DNA aptamer specifically targetsgastric cancer. Int J Biochem Cell Biol. 2014;46:1–8.

    Article  PubMed  Google Scholar 

  50. Sefah K, Meng L, Lopez-Colon D, Jimenez E, Liu C, Tan W. DNA aptamers as molecular probes for colorectal cancer study. PLoS ONE. 2010;5(12):e14269. doi:10.1371/journal.pone.0014269.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Dua P, Kang HS, Hong SM, Tsao MS, Kim S, Lee DK. Alkaline phosphatase ALPPL-2 is a novel pancreatic carcinoma-associated protein. Cancer Res. 2013;73(6):1934–45. doi:10.1158/0008-5472.CAN-12-3682.

    Article  CAS  PubMed  Google Scholar 

  52. Sefah K, Tang ZW, Shangguan DH, Chen H, Lopez-Colon D, Li Y, et al. Molecular recognition of acute myeloid leukemia using aptamers. Leukemia. 2009;23(2):235–44. doi:10.1038/leu.2008.335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Pasikanti KK, Esuvaranathan K, Ho PC, Mahendran R, Kamaraj R, Wu QH, et al. Noninvasive urinary metabonomic diagnosis of human bladder cancer. J Proteome Res. 2010;9(6):2988–95. doi:10.1021/pr901173v.

    Article  CAS  PubMed  Google Scholar 

  54. Qin T, Liu H, Song Q, Song G, Wang HZ, Pan YY, et al. The screening of volatile markers for hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev. 2010;19(9):2247–53. doi:10.1158/1055-9965.EPI-10-0302.

    Article  CAS  PubMed  Google Scholar 

  55. Wu H, Xue R, Tang Z, Deng C, Liu T, Zeng H, et al. Metabolomic investigation of gastric cancer tissue using gas chromatography/mass spectrometry. Anal Bioanal Chem. 2010;396(4):1385–95. doi:10.1007/s00216-009-3317-4.

    Article  CAS  PubMed  Google Scholar 

  56. Zhang Z, Qiu Y, Hua Y, Wang Y, Chen T, Zhao A, et al. Serum and urinary metabonomic study of human osteosarcoma. J Proteome Res. 2010;9(9):4861–8. doi:10.1021/pr100480r.

    Article  CAS  PubMed  Google Scholar 

  57. Barocas DA, Motley S, Cookson MS, Chang SS, Penson DF, Dai Q, et al. Oxidative stress measured by urine F2-isoprostane level is associated with prostate cancer. J Urol. 2011;185(6):2102–7. doi:10.1016/j.juro.2011.02.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kondo Y, Nishiumi S, Shinohara M, Hatano N, Ikeda A, Yoshie T, et al. Serum fatty acid profiling of colorectal cancer by gas chromatography/mass spectrometry. Biomark Med. 2011;5(4):451–60. doi:10.2217/bmm.11.41.

    Article  CAS  PubMed  Google Scholar 

  59. Buszewski B, Ulanowska A, Kowalkowski T, Cieslinski K. Investigation of lung cancer biomarkers by hyphenated separation techniques and chemometrics. Clin Chem Lab Med. 2012;50(3):573–81. doi:10.1515/CCLM.2011.769.

    Article  CAS  Google Scholar 

  60. Cheng Y, Xie G, Chen T, Qiu Y, Zou X, Zheng M, et al. Distinct urinary metabolic profile of human colorectal cancer. J Proteome Res. 2012;11(2):1354–63. doi:10.1021/pr201001a.

    Article  CAS  PubMed  Google Scholar 

  61. Nishiumi S, Kobayashi T, Ikeda A, Yoshie T, Kibi M, Izumi Y, et al. A novel serum metabolomics-based diagnostic approach for colorectal cancer. PLoS ONE. 2012;7(7):e40459. doi:10.1371/journal.pone.0040459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Silva CL, Passos M, Camara JS. Solid phase microextraction, mass spectrometry and metabolomic approaches for detection of potential urinary cancer biomarkers—a powerful strategy for breast cancer diagnosis. Talanta. 2012;89:360–8. doi:10.1016/j.talanta.2011.12.041.

    Article  CAS  PubMed  Google Scholar 

  63. Xiao JF, Varghese RS, Zhou B, Nezami Ranjbar MR, Zhao Y, Tsai TH, et al. LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort. J Proteome Res. 2012;11(12):5914–23. doi:10.1021/pr300673x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Baniasadi H, Nagana Gowda GA, Gu H, Zeng A, Zhuang S, Skill N, et al. Targeted metabolic profiling of hepatocellular carcinoma and hepatitis C using LC-MS/MS. Electrophoresis. 2013;34:2910–7. doi:10.1002/elps.201300029.

    CAS  PubMed  Google Scholar 

  65. Dai W, Yin P, Chen P, Kong H, Luo P, Xu Z, et al. Study of urinary steroid hormone disorders: difference between hepatocellular carcinoma in early stage and cirrhosis. Anal Bioanal Chem. 2014;406:4325–35. doi:10.1007/s00216-014-7843-3.

    Article  CAS  PubMed  Google Scholar 

  66. Fitian AI, Nelson DR, Liu C, Xu Y, Ararat M, Cabrera R. Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS-MS. Liver int : off j of the Int Assoc for the Study of the Liver. 2014. doi:10.1111/liv.12541.

    Google Scholar 

  67. Phua LC, Chue XP, Koh PK, Cheah PY, Ho HK, Chan EC. Non-invasive fecal metabonomic detection of colorectal cancer. Cancer biology & ther. 2014;15(4):389–97. doi:10.4161/cbt.27625.

    Article  CAS  Google Scholar 

  68. Qiu Y, Cai G, Zhou B, Li D, Zhao A, Xie G, et al. A distinct metabolic signature of human colorectal cancer with prognostic potential. Clin cancer res : an off j of the Am Assoc for Cancer Res. 2014;20(8):2136–46. doi:10.1158/1078-0432.CCR-13-1939.

    Article  CAS  Google Scholar 

  69. Jin X, Yun SJ, Jeong P, Kim IY, Kim WJ, Park S. Diagnosis of bladder cancer and prediction of survival by urinary metabolomics. Oncotarget. 2014;5:1635–45.

    PubMed  PubMed Central  Google Scholar 

  70. Daniels DA, Chen H, Hicke BJ, Swiderek KM, Gold L. A tenascin-C aptamer identified by tumor cell SELEX: systematic evolution of ligands by exponential enrichment. Proc Natl Acad Sci U S A. 2003;100(26):15416–21. doi:10.1073/pnas.2136683100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ferreira CS, Papamichael K, Guilbault G, Schwarzacher T, Gariepy J, Missailidis S. DNA aptamers against the MUC1 tumour marker: design of aptamer-antibody sandwich ELISA for the early diagnosis of epithelial tumours. Anal Bioanal Chem. 2008;390(4):1039–50. doi:10.1007/s00216-007-1470-1.

    Article  CAS  PubMed  Google Scholar 

  72. Shangguan D, Cao Z, Meng L, Mallikaratchy P, Sefah K, Wang H, et al. Cell-specific aptamer probes for membrane protein elucidation in cancer cells. J Proteome Res. 2008;7(5):2133–9. doi:10.1021/pr700894d.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Xiao Z, Shangguan D, Cao Z, Fang X, Tan W. Cell-specific internalization study of an aptamer from whole cell selection. Chemistry. 2008;14(6):1769–75. doi:10.1002/chem.200701330.

    Article  CAS  PubMed  Google Scholar 

  74. Li S, Xu H, Ding H, Huang Y, Cao X, Yang G, et al. Identification of an aptamer targeting hnRNP A1 by tissue slide-based SELEX. J Pathol. 2009;218(3):327–36. doi:10.1002/path.2543.

    Article  CAS  PubMed  Google Scholar 

  75. Somasunderam A, Thiviyanathan V, Tanaka T, Li X, Neerathilingam M, Lokesh GL, et al. Combinatorial selection of DNA thioaptamers targeted to the HA binding domain of human CD44. Biochemistry. 2010;49(42):9106–12. doi:10.1021/bi1009503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Savory N, Abe K, Sode K, Ikebukuro K. Selection of DNA aptamer against prostate specific antigen using a genetic algorithm and application to sensing. Biosens Bioelectron. 2010;26(4):1386–91. doi:10.1016/j.bios.2010.07.057.

    Article  CAS  PubMed  Google Scholar 

  77. Ray P, Rialon-Guevara KL, Veras E, Sullenger BA, White RR. Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker. J Clin Invest. 2012;122(5):1734–41. doi:10.1172/JCI62385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Simmons SC, McKenzie EA, Harris LK, Aplin JD, Brenchley PE, Velasco-Garcia MN, et al. Development of novel single-stranded nucleic acid aptamers against the pro-angiogenic and metastatic enzyme heparanase (HPSE1). PLoS ONE. 2012;7(6):e37938. doi:10.1371/journal.pone.0037938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Sefah K, Bae KM, Phillips JA, Siemann DW, Su Z, McClellan S, et al. Cell-based selection provides novel molecular probes for cancer stem cells. Int J Cancer. 2013;132(11):2578–88. doi:10.1002/ijc.27936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shigdar S, Qiao L, Zhou SF, Xiang D, Wang T, Li Y, et al. RNA aptamers targeting cancer stem cell marker CD133. Cancer Lett. 2013;330(1):84–95. doi:10.1016/j.canlet.2012.11.032.

    Article  CAS  PubMed  Google Scholar 

  81. 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. doi:10.1016/j.bios.2013.05.024.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript. This work was supported, in part, by grants from the National Natural Science Foundation of China (81172329 and 81372644), the Chinese National High Tech Program (2012AA02A504, 2012AA02A203, and 2011ZX09307-001-05), Shanghai Excellent Academic Leader Plan (11XD1403600), Cross-Biomedical-Engineering Project of Shanghai Jiao Tong University, and International Cooperative Project from Shanghai Science and Technology Commission (12410706400).

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  1. Department of Surgery, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Ruijin er Road, No. 197, 200025, Shanghai, China

    Yinan Chen, Zhenggang Zhu & Yingyan Yu

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  1. Yinan Chen
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Correspondence to Zhenggang Zhu or Yingyan Yu.

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Chen, Y., Zhu, Z. & Yu, Y. Novel methodologies in analysis of small molecule biomarkers and living cells. Tumor Biol. 35, 9469–9477 (2014). https://doi.org/10.1007/s13277-014-2439-2

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