Body fluid proteomics: Prospects for biomarker discovery

Many diseases are caused by perturbations of cellular signaling pathways and related pathway networks as a result of genetic aberrations. These perturbations are manifested by altered cellular protein profiles in the fluids bathing tissue/organs (i.e., the tissue interstitial fluid, TIF). A major challenge of clinical chemistry is to quantitatively map these perturbed protein profiles – the so‐called “signatures of disease” – using modern proteomic technologies. This information can be utilized to design protein biomarkers for the early detection of disease, monitoring disease progression and efficacy of drug action. Here, we discuss the use of body fluids in the context of prospective biomarker discovery, and the marked 1000–1500‐fold dilution of body fluid proteins, during their passage from TIF to the circulatory system. Further, we discuss proteomics strategies aimed at depleting major serum proteins, especially albumin, in order to focus on low‐abundance protein/peptides in plasma. A major limitation of depletion strategies is the removal of low‐molecular weight protein/peptides which specifically bind major plasma proteins. We present a prototype model, using albumin, for understanding the multifaceted nature of biomarker research, highlighting the involvement of albumin in Alzheimer's disease. This model underscores the need for a system‐level understanding for biomarker research and personalized medicine.

[1]  G. Hortin,et al.  Diagnostic potential for urinary proteomics. , 2007, Pharmacogenomics.

[2]  H. Dihazi,et al.  Urinary proteomics: a tool to discover biomarkers of kidney diseases , 2007, Expert review of proteomics.

[3]  Eugene A. Kapp,et al.  Enhanced analysis of the mouse plasma proteome using cysteine-containing tryptic glycopeptides. , 2007, Journal of proteome research.

[4]  G. Opiteck,et al.  An investigation of plasma collection, stabilization, and storage procedures for proteomic analysis of clinical samples , 2004, Clinical Proteomics.

[5]  V. Thongboonkerd.  Proteomics of Human Body Fluids , 2007 .

[6]  V. Thongboonkerd.  Proteomics of human body fluids : principles, methods, and applications , 2007 .

[7]  Sung‐Min Ahn,et al.  Proteomic Strategies for Analyzing Body Fluids , 2007 .

[8]  Rebekah L. Gundry,et al.  Investigation of an albumin‐enriched fraction of human serum and its albuminome , 2007, Proteomics. Clinical applications.

[9]  D. T. Wong,et al.  Human body fluid proteome analysis , 2006, Proteomics.

[10]  D. Dickson,et al.  Filling the Gaps in the Aβ Cascade Hypothesis of Alzheimers Disease , 2006 .

[11]  G. Omenn.  Exploring the Human Plasma Proteome: OMENN:HUMAN PLASMA PROTEO O-BK , 2006 .

[12]  J. Nicholson.  Global systems biology, personalized medicine and molecular epidemiology , 2006, Molecular systems biology.

[13]  E. Diamandis.  Peptidomics for cancer diagnosis: present and future. , 2006, Journal of proteome research.

[14]  Matthias Mann,et al.  Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors , 2006, Genome Biology.

[15]  Amanda Paulovich,et al.  Cancer biomarkers: a systems approach , 2006, Nature Biotechnology.

[16]  J. Brand,et al.  Depletion efficiency and recovery of trace markers from a multiparameter immunodepletion column , 2006, Proteomics.

[17]  Christopher M. Overall,et al.  Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy , 2006, Nature Reviews Cancer.

[18]  Christopher M. Overall,et al.  Degradomics: Systems biology of the protease web. Pleiotropic roles of MMPs in cancer , 2006, Cancer and Metastasis Reviews.

[19]  Guanghui Wang,et al.  Comparative study of three proteomic quantitative methods, DIGE, cICAT, and iTRAQ, using 2D gel- or LC-MALDI TOF/TOF. , 2006, Journal of Proteome Research.

[20]  E. Petricoin,et al.  Serum peptidome for cancer detection: spinning biologic trash into diagnostic gold. , 2005, The Journal of clinical investigation.

[21]  A. Olshen,et al.  Differential exoprotease activities confer tumor-specific serum peptidome patterns. , 2005, The Journal of clinical investigation.

[22]  X. Bossuyt.  Advances in serum protein electrophoresis. , 2006, Advances in clinical chemistry.

[23]  Matthias Mann,et al.  Large-scale and high-confidence proteomic analysis of human seminal plasma , 2006, Genome Biology.

[24]  T. Pawlik,et al.  Proteomic analysis of nipple aspirate fluid from women with early-stage breast cancer using isotope-coded affinity tags and tandem mass spectrometry reveals differential expression of vitamin D binding protein , 2006, BMC Cancer.

[25]  J. Weinstein,et al.  Biomarkers in Cancer Staging, Prognosis and Treatment Selection , 2005, Nature Reviews Cancer.

[26]  K. Resing,et al.  Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun Proteomics*S , 2005, Molecular & Cellular Proteomics.

[27]  R. Iozzo,et al.  The role of proteomics in the assessment of premature rupture of fetal membranes. , 2005, Clinica chimica acta; international journal of clinical chemistry.

[28]  M. Mann,et al.  Mass spectrometry–based proteomics turns quantitative , 2005, Nature chemical biology.

[29]  E. Petricoin,et al.  Analysis of albumin-associated peptides and proteins from ovarian cancer patients. , 2005, Clinical chemistry.

[30]  Graham B. I. Scott,et al.  HUPO Plasma Proteome Project specimen collection and handling: Towards the standardization of parameters for plasma proteome samples , 2005, Proteomics.

[31]  Eugene A. Kapp,et al.  Application of 2‐D free‐flow electrophoresis/RP‐HPLC for proteomic analysis of human plasma depleted of multi high‐abundance proteins , 2005, Proteomics.

[32]  G. Omenn,et al.  Exploring the Human Plasma Proteome , 2005, Proteomics.

[33]  Gilbert S Omenn,et al.  An evaluation, comparison, and accurate benchmarking of several publicly available MS/MS search algorithms: Sensitivity and specificity analysis , 2005, Proteomics.

[34]  C. V. Jongeneel,et al.  An atlas of human gene expression from massively parallel signature sequencing (MPSS). , 2005, Genome research.

[35]  Robert J Beynon,et al.  Metabolic Labeling of Proteins for Proteomics* , 2005, Molecular & Cellular Proteomics.

[36]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[37]  Hsin-Yi Wu,et al.  Proteomic profiling of human pleural effusion using two-dimensional nano liquid chromatography tandem mass spectrometry. , 2005, Journal of proteome research.

[38]  W. Su,et al.  Proteomic analysis of human pleural effusion , 2005, Proteomics.

[39]  R. Wattiez,et al.  Proteomics of bronchoalveolar lavage fluid. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[40]  Francesca Antonucci,et al.  Numerical approaches for quantitative analysis of two‐dimensional maps: A review of commercial software and home‐made systems , 2005, Proteomics.

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

[42]  P. Davidsson,et al.  Comparison of different depletion strategies for improved resolution in proteomic analysis of human serum samples , 2005, Proteomics.

[43]  Egisto Boschetti,et al.  Prefractionation techniques in proteome analysis: The mining tools of the third millennium , 2005, Electrophoresis.

[44]  B. Kasravi,et al.  Understanding and interpreting serum protein electrophoresis. , 2005, American family physician.

[45]  H. Langen,et al.  Depletion of the high-abundance plasma proteins , 2004, Amino Acids.

[46]  R. Molina,et al.  Clinical Evaluation of the Simultaneous Determination of Tumor Markers in Fluid and Serum and Their Ratio in the Differential Diagnosis of Serous Effusions , 2004, Tumor Biology.

[47]  Kathryn S Lilley,et al.  All about DIGE: quantification technology for differential-display 2D-gel proteomics , 2004, Expert review of proteomics.

[48]  K. Parker,et al.  Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents*S , 2004, Molecular & Cellular Proteomics.

[49]  J. van der Greef,et al.  The role of analytical sciences in medical systems biology. , 2004, Current opinion in chemical biology.

[50]  Troels Z. Kristiansen,et al.  Comprehensive proteomic analysis of human pancreatic juice. , 2004, Journal of proteome research.

[51]  Eugene A. Kapp,et al.  A proteome strategy for fractionating proteins and peptides using continuous free-flow electrophoresis coupled off-line to reversed-phase high-performance liquid chromatography. , 2004, Analytical chemistry.

[52]  Bart N Lambrecht,et al.  Proteomic analysis of exosomes isolated from human malignant pleural effusions. , 2004, American journal of respiratory cell and molecular biology.

[53]  J. Yates,et al.  A model for random sampling and estimation of relative protein abundance in shotgun proteomics. , 2004, Analytical chemistry.

[54]  B. Zlokovic.  Clearing amyloid through the blood–brain barrier , 2004, Journal of neurochemistry.

[55]  Rui Vitorino,et al.  Identification of human whole saliva protein components using proteomics , 2004, Proteomics.

[56]  K. Sandelin,et al.  Proteomic Characterization of the Interstitial Fluid Perfusing the Breast Tumor Microenvironment , 2004, Molecular & Cellular Proteomics.

[57]  E. Diamandis.  Mass Spectrometry as a Diagnostic and a Cancer Biomarker Discovery Tool , 2004, Molecular & Cellular Proteomics.

[58]  Hanno Langen,et al.  How Industry Is Approaching the Search for New Diagnostic Markers and Biomarkers* , 2004, Molecular & Cellular Proteomics.

[59]  N. Blom,et al.  Feature-based prediction of non-classical and leaderless protein secretion. , 2004, Protein engineering, design & selection : PEDS.

[60]  Leroy Hood,et al.  Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine. , 2004, Journal of proteome research.

[61]  Marija Mihailovich,et al.  Translational regulation of BACE-1 expression in neuronal and non-neuronal cells. , 2004, Nucleic acids research.

[62]  E. Petricoin,et al.  Proteomic analysis of lymph , 2004, Proteomics.

[63]  F. Regnier,et al.  Quantification in proteomics through stable isotope coding: a review. , 2004, Journal of proteome research.

[64]  M. Oleksiewicz.  Stool protein analysis by two‐dimensional gel electrophoresis and mass spectrometry , 2004, Scandinavian journal of gastroenterology.

[65]  Emanuel F. Petricoin,et al.  Clinical Applications of Proteomics: Proteomic Pattern Diagnostics , 2002, Journal of Mammary Gland Biology and Neoplasia.

[66]  Matej Oresic,et al.  Methods for the differential integrative omic analysis of plasma from a transgenic disease animal model. , 2004, Omics : a journal of integrative biology.

[67]  Emanuel F. Petricoin,et al.  Biomarker Amplification by Serum Carrier Protein Binding , 2004, Disease markers.

[68]  M. Ferrari,et al.  Clinical proteomics: Written in blood , 2003, Nature.

[69]  Somasekar Seshagiri,et al.  The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. , 2003, Genome research.

[70]  T. Veenstra,et al.  Characterization of the Low Molecular Weight Human Serum Proteome*S , 2003, Molecular & Cellular Proteomics.

[71]  B. Dastugue,et al.  Identification of biologic markers of the premature rupture of fetal membranes: Proteomic approach , 2003, Proteomics.

[72]  S. Hunt,et al.  Multiplex proteomic analysis by two‐dimensional differential in‐gel electrophoresis , 2003, Proteomics.

[73]  Ruedi Aebersold,et al.  Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry , 2003, Nature Biotechnology.

[74]  Zheng Yuan,et al.  The mouse secretome: functional classification of the proteins secreted into the extracellular environment. , 2003, Genome research.

[75]  J. Hirabayashi,et al.  Lectin affinity capture, isotope-coded tagging and mass spectrometry to identify N-linked glycoproteins , 2003, Nature Biotechnology.

[76]  P. Kemmeren,et al.  Monitoring global messenger RNA changes in externally controlled microarray experiments , 2003, EMBO reports.

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

[78]  N. Anderson,et al.  Multi‐component immunoaffinity subtraction chromatography: An innovative step towards a comprehensive survey of the human plasma proteome , 2003, Proteomics.

[79]  E. Petricoin,et al.  Early detection: Proteomic applications for the early detection of cancer , 2003, Nature Reviews Cancer.

[80]  A. van Dalen,et al.  Comparative analysis of CA125, tissue polypeptide specific antigen, and soluble interleukin‐2 receptor α levels in sera, cyst, and ascitic fluids from patients with ovarian carcinoma , 2002, Cancer.

[81]  Hans-Jürgen Thiesen,et al.  Mass spectrometric proteome analyses of synovial fluids and plasmas from patients suffering from rheumatoid arthritis and comparison to reactive arthritis or osteoarthritis , 2002, Electrophoresis.

[82]  D. Schenk,et al.  The role of microglia in Alzheimer’s disease: friend or foe? , 2002, Neurobiology of Aging.

[83]  E. Petricoin,et al.  Clinical proteomics: translating benchside promise into bedside reality , 2002, Nature Reviews Drug Discovery.

[84]  L. Zitvogel,et al.  Malignant effusions and immunogenic tumour-derived exosomes , 2002, The Lancet.

[85]  C. López-Otín,et al.  Protease degradomics: A new challenge for proteomics , 2002, Nature Reviews Molecular Cell Biology.

[86]  M. Mann,et al.  Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics* , 2002, Molecular & Cellular Proteomics.

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

[88]  C. Masters,et al.  Pharmacological knock-down of the presenilin 1 heterodimer by a novel gamma -secretase inhibitor: implications for presenilin biology. , 2001, The Journal of biological chemistry.

[89]  E. Kojro,et al.  Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

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

[91]  J. Little,et al.  Systematic review of epidemiological studies on meat, dairy products and egg consumption and risk of colorectal adenomas. , 2000, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

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

[93]  L. Tjernberg,et al.  Endogenous proteins controlling amyloid beta-peptide polymerization. Possible implications for beta-amyloid formation in the central nervous system and in peripheral tissues. , 1999, The Journal of biological chemistry.

[94]  N. Blanckaert,et al.  Serum protein electrophoresis and immunofixation by a semiautomated electrophoresis system. , 1998, Clinical chemistry.

[95]  M. Mattson.  Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. , 1997, Physiological reviews.

[96]  M. Ünlü,et al.  Difference gel electrophoresis. A single gel method for detecting changes in protein extracts , 1997, Electrophoresis.

[97]  T. Peters,et al.  All About Albumin: Biochemistry, Genetics, and Medical Applications , 1995 .

[98]  T. Waldmann,et al.  Renal handling of low molecular weight proteins. I. L-Chain metabolism in experimental renal disease. , 1971, The Journal of clinical investigation.

[99]  A. Guyton,et al.  Textbook of Medical Physiology , 1961 .

[100]  R. Weinberg,et al.  The Biology of Cancer , 2006 .

[101]  A. Tiselius,et al.  Electrophoresis of serum globulin: Electrophoretic analysis of normal and immune sera. , 1937, The Biochemical journal.