Clinical Proteomics for Cancer Biomarker Discovery and Therapeutic Targeting

As we emerge into the post-genome era, proteomics finds itself as the driving force field as we translate the nucleic acid information archive into understanding how the cell actually works and how disease processes operate. Even so, the traditionally held view of proteomics as simply cataloging and developing lists of the cellular protein repertoire of a cell are now changing, especially in the sub-discipline of clinical proteomics. The most relevant information archive to clinical applications and drug development involves the elucidation of the information flow of the cell; the “software” of protein pathway networks and circuitry. The deranged circuitry of the cell as the drug target itself as well as the effect of the drug on not just the target, but also the entire network, is what we now are striving towards. Clinical proteomics, as a new and most exciting sub-discipline of proteomics, involves the bench-to-bedside clinical application of proteomic tools. Unlike the genome, there are potentially thousands of proteomes: each cell type has its own unique proteome. Moreover, each cell type can alter its proteome depending on the unique tissue microenvironment in which it resides, giving rise to multiple permutations of a single proteome. Since there is no polymerase chain reaction equivalent to proteomics- identifying and discovering the “wiring diagram” of a human diseased cell in a biopsy specimen remains a daunting challenge. New micro-proteomic technologies are being and still need to be developed to drill down into the proteomes of clinically relevant material. Cancer, as a model disease, provides a fertile environment to study the application of proteomics at the bedside. The promise of clinical proteomics and the new technologies that are developed is that we will detect cancer earlier through discovery of biomarkers, we will discover the next generation of targets and imaging biomarkers, and we can then apply this knowledge to patient-tailored therapy.

[1]  P. O’Farrell.  High resolution two-dimensional electrophoresis of proteins. , 1975, The Journal of biological chemistry.

[2]  M E Belov,et al.  High-throughput proteomics using high-efficiency multiple-capillary liquid chromatography with on-line high-performance ESI FTICR mass spectrometry. , 2001, Analytical chemistry.

[3]  M. Karas,et al.  Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. , 1990, Methods in enzymology.

[4]  B. Chait,et al.  Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome , 2001, Nature Biotechnology.

[5]  J. Klose.  Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues , 1975, Humangenetik.

[6]  F. Lottspeich,et al.  Proteomics--a new way for drug target discovery. , 1998, Arzneimittel-Forschung.

[7]  G. Li,et al.  An integrated approach utilizing artificial neural networks and SELDI mass spectrometry for the classification of human tumours and rapid identification of potential biomarkers , 2002, Bioinform..

[8]  Robert F. Bonner,et al.  Laser Capture Microdissection: Molecular Analysis of Tissue , 1997, Science.

[9]  M. Stoeckli,et al.  Imaging mass spectrometry: A new technology for the analysis of protein expression in mammalian tissues , 2001, Nature Medicine.

[10]  E. Petricoin,et al.  New technologies for biomarker analysis of prostate cancer progression: Laser capture microdissection and tissue proteomics. , 2001, Urology.

[11]  E. Petricoin,et al.  Clinical proteomics: personalized molecular medicine. , 2001, JAMA.

[12]  A. Monks,et al.  Glutathione-associated enzymes in the human cell lines of the National Cancer Institute Drug Screening Program. , 1996, Molecular pharmacology.

[13]  Pierre Thibault,et al.  Rapid and sensitive separation of trace level protein digests using microfabricated devices coupled to a quadrupole ‐ time‐of‐flight mass spectrometer , 2000, Electrophoresis.

[14]  B. Chait,et al.  Automatic identification of proteins with a MALDI-quadrupole ion trap mass spectrometer. , 2001, Analytical chemistry.

[15]  A. Görg,et al.  The current state of two‐dimensional electrophoresis with immobilized pH gradients , 2000, Electrophoresis.

[16]  The International HapMap Consortium,et al.  A physical map of the human genome , 2001 .

[17]  K Matsubara,et al.  Expression profiles of active genes in human and mouse livers. , 1996, Gene.

[18]  H. Kato,et al.  Two‐dimensional polyacrylamide gel electrophoresis of human lung cancer: Qualitative aspects of tissue preparation in relation to histopathology , 1991, Electrophoresis.

[19]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[20]  P. Lapuerta,et al.  Neural Network Assessment of Perioperative Cardiac Risk in Vascular Surgery Patients , 1998, Medical decision making : an international journal of the Society for Medical Decision Making.

[21]  T. Rabilloud.  Two‐dimensional gel electrophoresis in proteomics: Old, old fashioned, but it still climbs up the mountains , 2002, Proteomics.

[22]  M J O'Hare,et al.  Proteomic definition of normal human luminal and myoepithelial breast cells purified from reduction mammoplasties. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[23]  E. Kohn,et al.  Proteomic analysis and identification of new biomarkers and therapeutic targets for invasive ovarian cancer , 2002, Proteomics.

[24]  T. Yip,et al.  New desorption strategies for the mass spectrometric analysis of macromolecules , 1993 .

[25]  E. Petricoin,et al.  Cancer proteomics: from biomarker discovery to signal pathway profiling. , 2001, Cancer journal.

[26]  D. Mccormick.  Sequence the Human Genome , 1986, Bio/Technology.

[27]  J. Seilhamer,et al.  A comparison of selected mRNA and protein abundances in human liver , 1997, Electrophoresis.

[28]  E. Petricoin,et al.  Rapid protein display profiling of cancer progression directly from human tissue using a protein biochip , 2000 .

[29]  E. Petricoin,et al.  Proteomic analysis of laser capture microdissected human prostate cancer and in vitro prostate cell lines , 2000, Electrophoresis.

[30]  G. Wright,et al.  Proteinchip® surface enhanced laser desorption/ionization (SELDI) mass spectrometry: a novel protein biochip technology for detection of prostate cancer biomarkers in complex protein mixtures , 1999, Prostate Cancer and Prostatic Diseases.

[31]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[32]  A. Shevchenko,et al.  Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry , 1996, Nature.

[33]  J. Yates,et al.  Large-scale analysis of the yeast proteome by multidimensional protein identification technology , 2001, Nature Biotechnology.

[34]  D. Hochstrasser,et al.  The dynamic range of protein expression: A challenge for proteomic research , 2000, Electrophoresis.

[35]  S. Gygi,et al.  Quantitative analysis of complex protein mixtures using isotope-coded affinity tags , 1999, Nature Biotechnology.

[36]  M. Wilkins,et al.  Progress with gene‐product mapping of the Mollicutes: Mycoplasma genitalium , 1995, Electrophoresis.

[37]  J. Lindon,et al.  Metabonomics: a platform for studying drug toxicity and gene function , 2002, Nature Reviews Drug Discovery.

[38]  C. L. Chang,et al.  The relationship between the mass spectra of drugs and their biological activity--an application of artificial intelligence to chemistry. , 1975, Computers in biology and medicine.

[39]  S M Hanash,et al.  Biomedical applications of two‐dimensional electrophoresis using immobilized pH gradients: Current status , 2000, Electrophoresis.

[40]  I. Amster,et al.  Fourier Transform Mass Spectrometry , 1996 .

[41]  E. Petricoin,et al.  Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front , 2001, Oncogene.

[42]  S. Gygi,et al.  Correlation between Protein and mRNA Abundance in Yeast , 1999, Molecular and Cellular Biology.

[43]  J. Hudson,et al.  In vivo gene expression profile analysis of human breast cancer progression. , 1999, Cancer research.

[44]  Petricoin Ef rd,et al.  Cancer proteomics: from biomarker discovery to signal pathway profiling. , 2001, Cancer journal.

[45]  John R Yates,et al.  Analysis of quantitative proteomic data generated via multidimensional protein identification technology. , 2002, Analytical chemistry.

[46]  L. Edenbrandt,et al.  Myocardial SPET: artificial neural networks describe extent and severity of perfusion defects. , 1999, Clinical physiology.

[47]  G. Auer,et al.  Inhibition of extracellular signal‐regulated kinase1/2 activity of the breast cancer cell line MDA‐MB‐231 leads to major alterations in the pattern of protein expression , 2000, Electrophoresis.

[48]  Thomas P Conrads,et al.  The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification. , 2002, Biochemical and biophysical research communications.

[49]  T. Ørntoft,et al.  Gene expression profiling: monitoring transcription and translation products using DNA microarrays and proteomics , 2000, FEBS letters.

[50]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.

[51]  N. Goodman.  Biological data becomes computer literate: new advances in bioinformatics. , 2002, Current opinion in biotechnology.

[52]  R. Srinivasan,et al.  Ablation of polymers and biological tissue by ultraviolet lasers. , 1986, Science.

[53]  L. Liotta,et al.  Laser capture microdissection. , 2006, Methods in molecular biology.

[54]  K. Biemann.  Mass spectrometry of peptides and proteins. , 1992, Annual review of biochemistry.

[55]  K. Hahnenberger,et al.  Integrated genomic/proteomic analysis. , 1999, Analytical chemistry.

[56]  Ruedi Aebersold,et al.  Quantitative proteome analysis by solid-phase isotope tagging and mass spectrometry , 2002, Nature Biotechnology.

[57]  P. O’Farrell,et al.  Two-dimensional polyacrylamide gel electrophoretic fractionation. , 1977, Methods in cell biology.

[58]  D. Cahill,et al.  Protein and antibody arrays and their medical applications. , 2001, Journal of immunological methods.