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Published in: Tumor Biology 10/2014

01-10-2014 | Review

Novel methodologies in analysis of small molecule biomarkers and living cells

Authors: Yinan Chen, Zhenggang Zhu, Yingyan Yu

Published in: Tumor Biology | Issue 10/2014

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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.
Literature
1.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference 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.PubMed 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.PubMed
4.
go back to reference 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. 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.
5.
go back to reference 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.PubMed 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.PubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
23.
go back to reference 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]. 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].
28.
go back to reference 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. 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.
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
31.
33.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
35.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
36.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
38.
39.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
40.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
41.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
42.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
44.
go back to reference Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990;249(4968):505–10.CrossRefPubMed Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990;249(4968):505–10.CrossRefPubMed
47.
go back to reference 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. 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.
49.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
53.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
58.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
59.
go back to reference 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.CrossRef 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.CrossRef
62.
63.
64.
go back to reference 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.PubMed 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.PubMed
65.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
66.
go back to reference 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. 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.
67.
go back to reference 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.CrossRef 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.CrossRef
68.
go back to reference 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.CrossRef 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.CrossRef
69.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
71.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
75.
77.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
Metadata
Title
Novel methodologies in analysis of small molecule biomarkers and living cells
Authors
Yinan Chen
Zhenggang Zhu
Yingyan Yu
Publication date
01-10-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 10/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2439-2

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