Restructuring proteomics through verification.

Proteomics technologies have revolutionized cell biology and biochemistry by providing powerful new tools to characterize complex proteomes, multiprotein complexes and post-translational modifications. Although proteomics technologies could address important problems in clinical and translational cancer research, attempts to use proteomics approaches to discover cancer biomarkers in biofluids and tissues have been largely unsuccessful and have given rise to considerable skepticism. The National Cancer Institute has taken a leading role in facilitating the translation of proteomics from research to clinical application, through its Clinical Proteomic Technologies for Cancer. This article highlights the building of a more reliable and efficient protein biomarker development pipeline that incorporates three steps: discovery, verification and qualification. In addition, we discuss the merits of multiple reaction monitoring mass spectrometry, a multiplex targeted proteomics platform, which has emerged as a potentially promising, high-throughput protein biomarker measurements technology for preclinical 'verification'.

[1]  P. Shah,et al.  Multiplex immune serum biomarker profiling in sarcoidosis and systemic sclerosis , 2009, European Respiratory Journal.

[2]  Rod K. Nibbe,et al.  Approaches to biomarkers in human colorectal cancer: looking back, to go forward. , 2009, Biomarkers in medicine.

[3]  A. Coolen,et al.  The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients , 2009, Targeted Oncology.

[4]  Christopher R Kinsinger,et al.  Protein-based multiplex assays: mock presubmissions to the US Food and Drug Administration. , 2010, Clinical chemistry.

[5]  Jeffrey R. Whiteaker,et al.  The evolving role of mass spectrometry in cancer biomarker discovery , 2009, Cancer biology & therapy.

[6]  N. Anderson,et al.  A List of Candidate Cancer Biomarkers for Targeted Proteomics , 2006, Biomarker insights.

[7]  J. Bunkenborg,et al.  Up‐regulated Proteins in the Fluid Bathing the Tumour Cell Microenvironment as Potential Serological Markers for Early Detection of Cancer of the Breast , 2010, Molecular oncology.

[8]  Leigh Anderson,et al.  Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins* , 2006, Molecular & Cellular Proteomics.

[9]  Qin Fu,et al.  Comparison of multiplex immunoassay platforms. , 2010, Clinical chemistry.

[10]  E. Diamandis,et al.  The bottleneck in the cancer biomarker pipeline and protein quantification through mass spectrometry-based approaches: current strategies for candidate verification. , 2010, Clinical chemistry.

[11]  Leigh Anderson,et al.  Candidate‐based proteomics in the search for biomarkers of cardiovascular disease , 2005, The Journal of physiology.

[12]  F. Collins,et al.  Genomic medicine--an updated primer. , 2010, The New England journal of medicine.

[13]  A. Potti,et al.  Translating genomics into clinical practice: Applications in lung cancer , 2009, Current oncology reports.

[14]  Christopher R Kinsinger,et al.  Analytical validation of protein-based multiplex assays: a workshop report by the NCI-FDA interagency oncology task force on molecular diagnostics. , 2010, Clinical chemistry.

[15]  E. Bandrés,et al.  Proteomic analysis in cancer research: potential application in clinical use , 2006, Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico.

[16]  Ruth Etzioni,et al.  Early detection: The case for early detection , 2003, Nature Reviews Cancer.

[17]  Andrew N Hoofnagle,et al.  Quantification of thyroglobulin, a low-abundance serum protein, by immunoaffinity peptide enrichment and tandem mass spectrometry. , 2008, Clinical chemistry.

[18]  Yanhui Hu,et al.  Next generation high density self assembling functional protein arrays , 2008, Nature Methods.

[19]  P. Workman Strategies for treating cancers caused by multiple genome abnormalities: from concepts to cures? , 2003, Current opinion in investigational drugs.

[20]  G. Jayson,et al.  'Fit-for-purpose' validation of SearchLight multiplex ELISAs of angiogenesis for clinical trial use. , 2009, Journal of immunological methods.

[21]  Quantitative serum proteomics using dual stable isotope coding and nano LC-MS/MSMS. , 2009, Journal of proteome research.

[22]  Christoph H Borchers,et al.  Multi-site assessment of the precision and reproducibility of multiple reaction monitoring–based measurements of proteins in plasma , 2009, Nature Biotechnology.

[23]  Pei Wang,et al.  The interface between biomarker discovery and clinical validation: The tar pit of the protein biomarker pipeline , 2008, Proteomics. Clinical applications.

[24]  Emanuel Schwarz,et al.  Label-free LC-MS/MS quantitative proteomics for large-scale biomarker discovery in complex samples. , 2007, Journal of separation science.

[25]  Steven A Carr,et al.  Protein biomarker discovery and validation: the long and uncertain path to clinical utility , 2006, Nature Biotechnology.

[26]  Darryl B. Hardie,et al.  Mass spectrometric quantitation of peptides and proteins using Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA). , 2004, Journal of proteome research.

[27]  Thomas A Neubert,et al.  Super-SILAC for tumors and tissues , 2010, Nature Methods.

[28]  D R Mani,et al.  Developing multiplexed assays for troponin I and interleukin-33 in plasma by peptide immunoaffinity enrichment and targeted mass spectrometry. , 2009, Clinical chemistry.

[29]  Kermit K. Murray,et al.  Microfluidic chips for mass spectrometry-based proteomics. , 2009, Journal of mass spectrometry : JMS.