Mass Spectrometry Based Biomarker Discovery, Verification, and Validation--quality Assurance and Control of Protein Biomarker Assays

Overview

Journal Mol Oncol

Specialties Molecular Biology
Oncology

Date 2014 Apr 10

PMID 24713096

Citations 84

Authors

Carol E Parker

Christoph H Borchers

Affiliations

Soon will be listed here.

Abstract

In its early years, mass spectrometry (MS)-based proteomics focused on the cataloging of proteins found in different species or different tissues. By 2005, proteomics was being used for protein quantitation, typically based on "proteotypic" peptides which act as surrogates for the parent proteins. Biomarker discovery is usually done by non-targeted "shotgun" proteomics, using relative quantitation methods to determine protein expression changes that correlate with disease (output given as "up-or-down regulation" or "fold-increases"). MS-based techniques can also perform "absolute" quantitation which is required for clinical applications (output given as protein concentrations). Here we describe the differences between these methods, factors that affect the precision and accuracy of the results, and some examples of recent studies using MS-based proteomics to verify cancer-related biomarkers.

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References

Meng Z, Veenstra T . Targeted mass spectrometry approaches for protein biomarker verification. J Proteomics. 2011; 74(12):2650-9. DOI: 10.1016/j.jprot.2011.04.011. View

Bellei E, Bergamini S, Monari E, Fantoni L, Cuoghi A, Ozben T . High-abundance proteins depletion for serum proteomic analysis: concomitant removal of non-targeted proteins. Amino Acids. 2010; 40(1):145-56. DOI: 10.1007/s00726-010-0628-x. View

Krastins B, Prakash A, Sarracino D, Nedelkov D, Niederkofler E, Kiernan U . Rapid development of sensitive, high-throughput, quantitative and highly selective mass spectrometric targeted immunoassays for clinically important proteins in human plasma and serum. Clin Biochem. 2013; 46(6):399-410. PMC: 3779129. DOI: 10.1016/j.clinbiochem.2012.12.019. View

Anderson N, Anderson N . The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics. 2002; 1(11):845-67. DOI: 10.1074/mcp.r200007-mcp200. View

Liebler D, Zimmerman L . Targeted quantitation of proteins by mass spectrometry. Biochemistry. 2013; 52(22):3797-806. PMC: 3674507. DOI: 10.1021/bi400110b. View

Haab B, Paulovich A, Anderson N, Clark A, Downing G, Hermjakob H . A reagent resource to identify proteins and peptides of interest for the cancer community: a workshop report. Mol Cell Proteomics. 2006; 5(10):1996-2007. DOI: 10.1074/mcp.T600020-MCP200. View

Ahn Y, Shin P, Oh N, Park G, Kim H, Yoo J . A lectin-coupled, targeted proteomic mass spectrometry (MRM MS) platform for identification of multiple liver cancer biomarkers in human plasma. J Proteomics. 2012; 75(17):5507-15. DOI: 10.1016/j.jprot.2012.06.027. View

Craven R, Vasudev N, Banks R . Proteomics and the search for biomarkers for renal cancer. Clin Biochem. 2012; 46(6):456-65. DOI: 10.1016/j.clinbiochem.2012.11.029. View

Domanski D, Murphy L, Borchers C . Assay development for the determination of phosphorylation stoichiometry using multiple reaction monitoring methods with and without phosphatase treatment: application to breast cancer signaling pathways. Anal Chem. 2010; 82(13):5610-20. PMC: 2909760. DOI: 10.1021/ac1005553. View

10.

Cohen Freue G, Meredith A, Smith D, Bergman A, Sasaki M, Lam K . Computational biomarker pipeline from discovery to clinical implementation: plasma proteomic biomarkers for cardiac transplantation. PLoS Comput Biol. 2013; 9(4):e1002963. PMC: 3617196. DOI: 10.1371/journal.pcbi.1002963. View

11.

Hanash S, Baik C, Kallioniemi O . Emerging molecular biomarkers--blood-based strategies to detect and monitor cancer. Nat Rev Clin Oncol. 2011; 8(3):142-50. DOI: 10.1038/nrclinonc.2010.220. View

12.

Adkins J, Monroe M, Auberry K, Shen Y, Jacobs J, Camp 2nd D . A proteomic study of the HUPO Plasma Proteome Project's pilot samples using an accurate mass and time tag strategy. Proteomics. 2005; 5(13):3454-66. PMC: 2041806. DOI: 10.1002/pmic.200401333. View

13.

Chambers A, Percy A, Simon R, Borchers C . MRM for the verification of cancer biomarker proteins: recent applications to human plasma and serum. Expert Rev Proteomics. 2014; 11(2):137-48. DOI: 10.1586/14789450.2014.877346. View

14.

Paulovich A, Billheimer D, Ham A, Vega-Montoto L, Rudnick P, Tabb D . Interlaboratory study characterizing a yeast performance standard for benchmarking LC-MS platform performance. Mol Cell Proteomics. 2009; 9(2):242-54. PMC: 2830837. DOI: 10.1074/mcp.M900222-MCP200. View

15.

Nicol G, Han M, Kim J, Birse C, Brand E, Nguyen A . Use of an immunoaffinity-mass spectrometry-based approach for the quantification of protein biomarkers from serum samples of lung cancer patients. Mol Cell Proteomics. 2008; 7(10):1974-82. DOI: 10.1074/mcp.M700476-MCP200. View

16.

Percy A, Chambers A, Parker C, Borchers C . Absolute quantitation of proteins in human blood by multiplexed multiple reaction monitoring mass spectrometry. Methods Mol Biol. 2013; 1000:167-89. DOI: 10.1007/978-1-62703-405-0_13. View

17.

Surinova S, Schiess R, Huttenhain R, Cerciello F, Wollscheid B, Aebersold R . On the development of plasma protein biomarkers. J Proteome Res. 2010; 10(1):5-16. DOI: 10.1021/pr1008515. View

18.

Elliott M, Smith D, Parker C, Borchers C . Current trends in quantitative proteomics. J Mass Spectrom. 2009; 44(12):1637-60. DOI: 10.1002/jms.1692. View

19.

Wehr A, Hwang W, Blair I, Yu K . Relative quantification of serum proteins from pancreatic ductal adenocarcinoma patients by stable isotope dilution liquid chromatography-mass spectrometry. J Proteome Res. 2012; 11(3):1749-58. PMC: 3292696. DOI: 10.1021/pr201011f. View

20.

Cohen Freue G, Borchers C . Multiple reaction monitoring (MRM): principles and application to coronary artery disease. Circ Cardiovasc Genet. 2012; 5(3):378. DOI: 10.1161/CIRCGENETICS.111.959528. View