Top‐down proteomic analysis by MALDI‐TOF profiling: Concentration‐independent biomarkers

Although numerous protein biomarkers have been correlated with advanced disease states, no new clinical assays have been developed. Goals often anticipate disease‐specific protein changes that exceed values among healthy individuals, a property common to acute phase reactants. This review considers somewhat different approaches. It focuses on intact protein isoform ratios that present a biomarker without change in the total concentration of the protein. These will seldom be detected by peptide level analysis or by most antibody‐based assays. For example, application of an inexpensive method to large sample groups resulted in observation of several polymorphisms, including the first structural polymorphism of apolipoprotein C1. Isoform distribution of this protein was altered and was eventually linked to increased obesity. Numerous other protein isoforms included C‐ and N‐terminal proteolysis, changes of glycoisoform ratios and certain types of sulfhydryl oxidation. While many of these gave excellent statistical correlation with advanced disease, clinical utility was not apparent. More important may be that protein isoform ratios were very stable in each individual. Diagnosis by longitudinal analysis of the same individual might increase sensitivity of protein biomarkers by 20‐fold or more. Protein changes that exceed the range of values found among healthy individuals may be uncommon.

[1]  C. Berne,et al.  Plasma proteome changes in subjects with Type 2 diabetes mellitus with a low or high early insulin response. , 2008, Clinical science.

[2]  Laura Beretta,et al.  Proteomics from the clinical perspective: many hopes and much debate , 2007, Nature Methods.

[3]  G. Nelsestuen,et al.  Correlation of a T45S variant of apolipoprotein C1 with elevated BMI in persons of American Indian and Mexican ancestries , 2007, International Journal of Obesity.

[4]  I. Idris,et al.  Dipeptidyl peptidase‐IV inhibitors: a major new class of oral antidiabetic drug , 2007, Diabetes, obesity & metabolism.

[5]  M. Baker,et al.  Evaluation of endogenous plasma peptide extraction methods for mass spectrometric biomarker discovery. , 2007, Journal of proteome research.

[6]  C. Skibola,et al.  Screening the human serum proteome for genotype–phenotype associations: An analysis of the IL6 –174G>C polymorphism , 2007, Proteomics.

[7]  R. Wevers,et al.  Transferrin and apolipoprotein C-III isofocusing are complementary in the diagnosis of N- and O-glycan biosynthesis defects. , 2007, Clinical chemistry.

[8]  G. Nelsestuen,et al.  Potential biomarkers of an exaggerated response to endotoxemia , 2007, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[9]  G. Nelsestuen,et al.  A functional polymorphism of apolipoprotein C1 detected by mass spectrometry , 2006, The FEBS Journal.

[10]  Werner Zolg,et al.  The Proteomic Search for Diagnostic Biomarkers , 2006, Molecular & Cellular Proteomics.

[11]  G. Nelsestuen,et al.  Studying multiple protein profiles over time to assess biomarker validity , 2006, Expert review of proteomics.

[12]  N. Bergeron,et al.  Apolipoprotein C-III isoforms: kinetics and relative implication in lipid metabolism Published, JLR Papers in Press, February 22, 2006. , 2006, Journal of Lipid Research.

[13]  Melinda E. Lull,et al.  Apo-AII is an elevated biomarker of chronic non-human primate ethanol self-administration. , 2006, Alcohol and alcoholism.

[14]  Jos H Beijnen,et al.  Identification of serum proteins discriminating colorectal cancer patients and healthy controls using surface-enhanced laser desorption ionisation-time of flight mass spectrometry. , 2006, World journal of gastroenterology.

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

[16]  Kym Faull,et al.  Characterization of serum biomarkers for detection of early stage ovarian cancer , 2005, Proteomics.

[17]  A. Sinaiko,et al.  Plasma protein profiling: Unique and stable features of individuals , 2005, Proteomics.

[18]  N. Anderson,et al.  The Roles of Multiple Proteomic Platforms in a Pipeline for New Diagnostics , 2005, Molecular & Cellular Proteomics.

[19]  Xiao-Ying Meng,et al.  Classification of cancer types by measuring variants of host response proteins using SELDI serum assays , 2005, International journal of cancer.

[20]  T. Manabe,et al.  Direct targeting of human plasma for matrix‐assisted laser desorption/ionization and analysis of plasma proteins by time of flight‐mass spectrometry , 2005, Electrophoresis.

[21]  P. Tempst,et al.  Correcting common errors in identifying cancer-specific serum peptide signatures. , 2005, Journal of proteome research.

[22]  K. Savik,et al.  Proteomic identification of human neutrophil alpha‐defensins in chronic lung allograft rejection , 2005, Proteomics.

[23]  D. Bar-Or,et al.  Cysteinylation of maternal plasma albumin and its association with intrauterine growth restriction , 2005, Prenatal diagnosis.

[24]  Jeffrey S. Morris,et al.  Signal in noise: evaluating reported reproducibility of serum proteomic tests for ovarian cancer. , 2005, Journal of the National Cancer Institute.

[25]  William E Grizzle,et al.  Serum levels of an isoform of apolipoprotein A-II as a potential marker for prostate cancer. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[26]  Michael P Washburn,et al.  Utilisation of proteomics datasets generated via multidimensional protein identification technology (MudPIT). , 2004, Briefings in functional genomics & proteomics.

[27]  H. R. Bergen,et al.  Identification of transthyretin variants by sequential proteomic and genomic analysis. , 2004, Clinical chemistry.

[28]  Jean-Charles Sanchez,et al.  ApoC‐I and ApoC‐III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke , 2004, Proteomics.

[29]  Jeffrey S. Morris,et al.  Reproducibility of SELDI-TOF protein patterns in serum: comparing datasets from different experiments , 2004, Bioinform..

[30]  S. Sengupta,et al.  In Vitro and in Vivo Interactions of Homocysteine with Human Plasma Transthyretin* , 2003, Journal of Biological Chemistry.

[31]  G. Nelsestuen,et al.  Mutagenesis of the γ-Carboxyglutamic Acid Domain of Human Factor VII to Generate Maximum Enhancement of the Membrane Contact Site* , 2003, The Journal of Biological Chemistry.

[32]  H. R. Bergen,et al.  On-line immunoaffinity-liquid chromatography-mass spectrometry for identification of amyloid disease markers in biological fluids. , 2003, Analytical chemistry.

[33]  R. Nelson,et al.  Detection of novel truncated forms of human serum amyloid A protein in human plasma , 2003, FEBS letters.

[34]  H. R. Bergen,et al.  An on-line assay for clinical detection of amyloidogenic transthyretin variants directly from serum , 2003, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[35]  C. Durinx,et al.  Dipeptidyl-Peptidase IV from Bench to Bedside: An Update on Structural Properties, Functions, and Clinical Aspects of the Enzyme DPP IV , 2003, Critical reviews in clinical laboratory sciences.

[36]  N. Anderson,et al.  The Human Plasma Proteome , 2002, Molecular & Cellular Proteomics.

[37]  B. Rockhill.  Proteomic patterns in serum and identification of ovarian cancer , 2002, The Lancet.

[38]  Douglas C Pearl,et al.  Proteomic patterns in serum and identification of ovarian cancer , 2002, The Lancet.

[39]  E. Petricoin,et al.  Use of proteomic patterns in serum to identify ovarian cancer , 2002, The Lancet.

[40]  H. R. Bergen,et al.  Online single-step analysis of blood proteins: the transferrin story. , 2001, Analytical biochemistry.

[41]  H. R. Bergen,et al.  Rapid determination of transferrin isoforms by immunoaffinity liquid chromatography and electrospray mass spectrometry. , 2001, Clinical chemistry.

[42]  G. Nelsestuen.  Enhancement of vitamin-K-dependent protein function by modification of the gamma-carboxyglutamic acid domain: studies of protein C and factor VII. , 1999, Trends in cardiovascular medicine.

[43]  P. Bondarenko,et al.  Mass spectral study of polymorphism of the apolipoproteins of very low density lipoprotein. , 1999, Journal of lipid research.

[44]  D. Hoyt,et al.  The use of sodium dodecyl sulfate to model the apolipoprotein environment. Evidence for peptide-SDS complexes using pulsed-field-gradient NMR spectroscopy. , 1998, Biochimica et biophysica acta.

[45]  K. Weisgraber,et al.  Sequence-specific 1H NMR resonance assignments and secondary structure of human apolipoprotein C-I in the presence of sodium dodecyl sulfate. , 1998, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[46]  P. Stein,et al.  What do dysfunctional serpins tell us about molecular mobility and disease? , 1995, Nature Structural Biology.

[47]  A. von Eckardstein,et al.  Apolipoprotein C-III(Lys58----Glu). Identification of an apolipoprotein C-III variant in a family with hyperalphalipoproteinemia. , 1991, The Journal of clinical investigation.