Summary
The identification and eventual application of tumor markers in cancer screening, early detection, diagnosis, and prognosis is a continuing focus of significant translational cancer research. While many new candidate markers have been discovered and at least partly characterized, very few have found widespread clinical application limited presently to the use of CA-125 in ovarian cancer, CEA, primarily in colon cancer, and PSA in prostate cancer screening and patient monitoring. The rapidly emerging field of cancer genomics and proteomics, and their clinical translation as “molecular diagnosis” and “molecular medicine” are already beginning to transform the field, and the accelerating growth of information and technology in this research area will undoubtedly transform the field of tumor markers and their application in the near future leading to improved molecular tools for cancer diagnosis, prognosis, and treatment and ultimately, to the emergence of novel and more effective cancer therapies, including improved approaches for immunotherapy and cancer prevention strategies. Toward this goal, herein are described detailed methods and workflows for mass spectrometry-based biomarker discovery in serum/plasma utilizing two complementary approaches – matrix-assisted laser desorption ionization time of flight (MALDI-TOF) and nanoflow reversed-phase liquid chromatography (RPLC)-tandem mass spectrometry (MS/MS). These discovery workflows incorporate both abundant protein depletion and sample fractionation upstream of analytical mass spectrometry to optimize the identification and quantitation of lower abundant species.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Hauskrecht, M., Pelikan, R., Malehorn, D.E., Bigbee, W.L., Lotze, M.T., (2005) Feature selection for classification of SELDI-TOF-MS proteomic profiles. Appl. Bioinformatics 4, 227–246.
Pelikan, R., Bigbee, W.L., Malehorn, D.E., Lyons-Weiler, J., and Hauskrecht, M. (2007) Intersession reproducibility of mass spectrometry profiles and its effect on accuracy of multivariate classification models. Bioinformatics 23, 3065–3072.
Baggerly, K.A., Morris, J.S., Edmonson, S.R., and Coombes, K.R. (2005) Signal in noise: evaluating reported reproducibility of serum proteomic tests for ovarian cancer. J. Natl. Cancer Inst. 97, 307–309.
Tirumalai, R.S., Chan, K.C., Prieto, D.A., Issaq, H.J., Conrads, T.P., (2003) Characterization of the low molecular weight human serum proteome. Mol. Cell. Proteomics 2, 1096–1103.
Washburn, M.P., Wolters, D., and Yates J.R. III. (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat. Biotechnol. 19, 242–247.
McLerran, D., Grizzle, W.E., Feng, Z., Bigbee, W.L., Banez, L.L., (2008) Analytical validation of serum proteomic profiling for diagnosis of prostate cancer: sources of sample bias. Clin. Chem. 54, 44–52.
Traum, A.Z., Wells, M.P., Aivado, M., Libermann, T.A., Ramoni, M.F., (2006) SELDI-TOF MS of quadruplicate urine and serum samples to evaluate changes related to storage conditions. Proteomics 6, 1676–1680.
Villanueva, J., Philip, J., Chaparro, C.A., Li, Y., Toledo-Crow, R., (2005) Correcting common errors in identifying cancer-specific serum peptide signatures. J. Proteome Res. 4, 1060–1072.
Whistler, T., Rollin, D., and Vernon, S.D. (2007) A method for improving SELDI-TOF mass spectrometry data quality. Proteome Sci. 5, 4–14.
Seam, N., Gonzales, D.A., Kern, S.J., Hortin, G.L., Hoehn, G.T., Suffredini, A.F. (2007) Quality control of serum albumin depletion for proteomic analysis. Clin. Chem. 53, 1915–1920.
Sundsten, T., Eberhardson, M., Goransson, M., and Bergsten, P. (2006) The use of proteomics in identifying differentially expressed serum proteins in humans with type 2 diabetes. Proteome Sci. 4, 4–22.
Villanueva, J., Lawlor, K., Toledo-Crow, R., and Tempst, P. (2006) Automated serum peptide profiling. Nat. Protoc. 1, 880–891.
Aivado, M., Spentzos, D., Alterovitz, G., Out, H.H., Grall. F., (2005) Optimization and evaluation of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) with reversed-phase protein arrays for protein profiling. Clin. Chem. Lab. Med. 43, 133–140.
McLerran, D., Grizzle, W.E., Feng, Z., Thompson, I.M., Bigbee, W.L., (2008) SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer. Clin. Chem. 54, 53–60.
Baggerly, K.A., Coombes, K.R., and Morris, J.S. (2005) Bias, randomization and ovarian proteomic data: A reply to “Producers and Consumers.” Canc. Informatics 1, 9–14.
Semmes, O.J., Feng, Z., Adam, B.L., Banez, L.L., Bigbee, W.L., (2005) Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility. Clin. Chem. 51, 102–112.
Villanueva, J., Philip, J., DeNoyer, L., and Tempst, P. (2007) Data analysis of assorted serum peptidome profiles. Nat. Protoc. 2, 588–602.
Hendriks, M.M., Smit, S., Akkermans, W.L., Reijmers, T.H., Eilers, P.H., (2007) How to distinguish healthy from diseased? Classification strategy for mass spectrometry-based clinical proteomics. Proteomics 7, 3672–3680.
Wong, J.W., Cagney, G., and Cartwright, H.M. (2005) SpecAlign–processing and alignment of mass spectra datasets. Bioinformatics 21, 2088–2090.
Au, J.S.K., Cho, W.C.X., Yip, T.T., Yip, C., Zhu, H., (2007) Deep proteome profiling of sera from never-smoked lung cancer patients. Biomed. Pharmacother. 61, 570–577.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Hood, B., Malehorn, D., Conrads, T., Bigbee, W. (2009). Serum Proteomics Using Mass Spectrometry. In: Tainsky, M. (eds) Tumor Biomarker Discovery. Methods in Molecular Biology, vol 520. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-811-9_8
Download citation
DOI: https://doi.org/10.1007/978-1-60327-811-9_8
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60327-810-2
Online ISBN: 978-1-60327-811-9
eBook Packages: Springer Protocols