Abstract
There is a significant need for markers that are diagnostic of disease, particularly cancer. For these biomarkers to be useful they would need to be able to detect disease early in its progression with high sensitivity and specificity. Many approaches are being undertaken to attempt to find such biomarkers using the tools of systems biology, i.e., parallel measurement techniques including proteomics (parallel protein measurements). Often the premise behind such an approach was to cast a wide net and then design an assay for specific elements that were found to be diagnostic. One such approach has utilized matrix-assisted laser desorption/ionization-mass spectrometry to interrogate the low-molecular-weight component of serum (the fluid component of blood following clotting), the serum peptidome. This approach has the appealing characteristic of speed of analysis but has a number of shortcomings mostly due to signal:noise and mass resolution in some instruments, making peak analysis difficult. Of course, experimental design and statistical analysis have to be conducted with the system limitations in mind. These points have been addressed by others, but few have focused on a potentially larger issue with serum peptidome analysis — are the signals being measured informing us about the disease state directly or indirectly through measurement of another physiological process such as hemostatic dysregulation? This article will present evidence that points to careful measures of the serum peptidome revealing differences in clotting time in disease states and not direct measures of tumor proteolytic activity on blood proteins.
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References
Anderson L, Anderson NG (1977) High resolution two-dimensional electrophoresis of human plasma proteins. Proc Natl Acad Sci U S A 74:5421–5425
Baggerly KA, Morris JS, Coombes KR (2004) Reproducibility of SELDI-TOF protein patterns in serum: comparing datasets from different experiments. Bioinformatics 20:777–785
Baggerly KA, Morris JS, Edmonson SR, Coombes KR (2005) Signal in noise: evaluating reported reproducibility of serum proteomic tests for ovarian cancer. J Natl Cancer Inst 97:307–309
Courchesne PL, Jones MD, Robinson JH, Spahr CS, McCracken S, Bentley DL, Luethy R, Patterson SD (1998) Optimization of capillary chromatography ion trap-mass spectrometry for identification of gel-separated proteins. Electrophoresis 19:956–967
Cyr M, Lepage Y, Blais C Jr, Gervais N, Cugno M, Rouleau J-L, Adam A (2001) Bradykinin and des-Arg9-bradykinin metabolic pathways and kinetics of activation of human plasma. Am J Physiol Heart Circ Physiol 281:H275–H283
Davis MT, Lee TD (1998) Rapid protein identification using a microscale electrospray LC/MS system on an ion trap mass spectrometer. J Am Soc Mass Spectrom 9194–9201
Fung ET, Thulasiraman V, Weinberger SR, Dalmasso EA (2001) Protein biochips for differential profiling. Curr Opin Biotechnol 12:65–69
Gao WM, Kuick R, Orchekowski RP, Misek DE, Qiu J, Greenberg AK, Rom WN, Brenner DE, Omenn GS, Haab BB, Hanash SM (2005) Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis. BMC Cancer 5:110
Goldsmith GH (2001) Hemostatic changes in patients with malignancy. Int J Hematol 73:151–156
Gutfeld O, Prus D, Ackerman Z, Dishon S, Linke RP, Levin M, Urieli-Shoval S (2006) Expression of serum amyloid a, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis. J Histochem Cytochem 54:63–73
Johnson RS, Davis MT, Taylor JA, Patterson SD (2005) Informatics for protein identification by mass spectrometry. Methods 35:223–236
Koomen JM, Li D, Xiao LC, Liu TC, Coombes KR, Abbruzzese J, Kobayashi R (2005) Direct tandemmass spectrometry reveals limitations in protein profiling experiments for plasma biomarker discovery. J Proteome Res 4:972–981
Le L, Chi K, Tyldesley S, Flibotte S, Diamond DL, Kuzyk MA, Sadar MD (2005) Identification of serum amyloid A as a biomarker to distinguish prostate cancer patients with bone lesions. Clin Chem 51:695–707
Ledford-Kraemer M (2004) Pre-analytical variables part 1. The clotting times 4:2–7 (http://www.clot-ed.com/edit/documents/CTApr2004.pdf)
Licklider LJ, Thoreen CC, Peng J, Gygi SP (2002) Automation of nanoscale microcapillary liquid chromatography-tandem mass spectrometry with a vented column. Anal Chem 74:3076–3083
Liotta LA, Petricoin EF (2006) Serum peptidome for cancer detection: spinning biologic trash into diagnostic gold. J Clin Invest 116:26–30
Lowenthal MS, Mehta AI, Frogale K, Bandle RW, Araujo RP, Hood BL, Veenstra TD, Conrads TP, Goldsmith P, Fishman D, Petricoin EF 3rd, Liotta LA (2005) Analysis of albumin-associated peptides and proteins from ovarian cancer patients. Clin Chem 51:1933–1945
McGinley MD, Davis MT, Robinson JH, Spahr CS, Bures EJ, Beierle J, Mort J, Patterson SD (2000) A simplified device for protein identification by microcapillary gradient liquid chromatography-tandem mass spectrometry. Electrophoresis 21:1678–1684
Ostergaard M, Rasmussen HH, Nielsen HV, Vorum H, Orntoft TF, Wolf H, Celis JE (1997) Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation. Cancer Res 57:4111–4117
Owens CA Jr (2001) Ahistory of blood coagulation. In: Nichols WL, Bowie EJW (eds) Foundation for Medical Education and Research, Rochester
Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA (2002) Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359:572–577
Pieper R, Gatlin CL, Makusky AJ, Russo PS, Schatz CR, Miller SS, Su Q, McGrath AM, Estock MA, Parmar PP, Zhao M, Huang ST, Zhou J, Wang F, Esquer-Blasco R, Anderson NL, Taylor J, Steiner S (2003) The human serum proteome: display of nearly 3700 chromatographically separated protein spots on two-dimensional electrophoresis gels and identification of 325 distinct proteins. Proteomics 3:1345–1364
Price GC, Thompson SA, Kam PCA (2004) Tissue factor and tissue factor pathway inhibitor. Anaesthesia 59:483–492
Ransohoff DF (2005) Lessons from controversy: ovarian cancer screening and serum proteomics. J Natl Cancer Inst 97:315–319
Rose K, Bougueleret L, Baussant T, Bohm G, Botti P, Colinge J, Cusin I, Gaertner H, Gleizes A, Heller M, Jimenez S, Johnson A, Kussmann M, Menin L, Menzel C, Ranno F, Rodriguez-Tome P, Rogers J, Saudrais C, Villain M, Wetmore D, Bairoch A, Hochstrasser D (2004) Industrial-scale proteomics: from liters of plasma to chemically synthesized proteins. Proteomics 4:2125–2150
Schrader M, Schulz-Knappe P (2001) Peptidomics technologies for human body fluids. Trends Biotechnol 19[10 Suppl]:S55–S60
Sorace JM, Zhan M (2003) A data review and re-assessment of ovarian cancer serum proteomic profiling. BMC Bioinformatics 4:24
Tirumalai RS, Chan KC, Prieto DA, Issaq HJ, Conrads TP, Veenstra TD (2003) Characterization of the low molecular weight human serum proteome. Mol Cell Proteomics 2:1096–1103
Tolson J, Bogumil R, Brunst E, Beck H, Elsner R, Humeny A, Kratzin H, Deeg M, Kuczyk M, Mueller GA, Mueller CA, Flad T (2004) Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients. Lab Invest 84:845–856
Triplett DA (2000) Coagulation and bleeding disorders: review and update. Clin Chem 46:1260–1269
Trousseau A (1865) Phlegmasia alba dolens. In: Clinique Medicale de l’Hotel-Dieu de Paris. Vol. 3. New Sydenham Society, London, pp 94–96
Van Geest-Daalderop JH, Mulder AB, Boonman-de Winter LJ, Hoekstra MM, van den Besselaar AM (2005) Preanalytical variables and off-site blood collection: influences on the results of the prothrombin time/international normalized ratio test and implications for monitoring of oral anticoagulant therapy. Clin Chem 51:561–568
Vermeulen R, Lan Q, Zhang L, Gunn L, McCarthy D, Woodbury RL, McGuire M, Podust VN, Li G, Chatterjee N, Mu R, Yin S, Rothman N, Smith MT (2005) Decreased levels of CXC-chemokines in serum of benzeneexposed workers identified by array-based proteomics. Proc Natl Acad Sci U S A 102:17041–17046
Villanueva J, Philip J, Entenberg D, Chaparro CA, Tanwar MK, Holland EC, Tempst P (2004) Serum peptide profiling by magnetic particle-assisted, automated sample processing and MALDI-TOF mass spectrometry. Anal Chem 76:1560–1570
Villanueva J, Shaffer DR, Philip J, Chaparro CA, Erdjument-Bromage H, Olshen AB, Fleisher M, Lilja H, Brogi E, Boyd J, Sanchez-Carbayo M, Holland EC, Cordon-Cardo C, Scher HI, Tempst P (2006) Differential exoprotease activities confer tumor-specific serum peptidome patterns. J Clin Invest 116:271–284
Yokoi K, Shih LC, Kobayashi R, Koomen J, Hawke D, Li D, Hamilton SR, Abbruzzese JL, Coombes KR, Fidler IJ (2005) Serum amyloid A as a tumor marker in sera of nude mice with orthotopic human pancreatic cancer and in plasma of patients with pancreatic cancer. Int J Oncol 27:1361–1369
Zhang Z, Bast RC Jr, Yu Y, Li J, Sokoll LJ, Rai AJ, Rosenzweig JM, Cameron B, Wang YY, Meng XY, Berchuck A, Van Haaften-Day C, Hacker NF, de Bruijn HW, van derZee AG, Jacobs IJ, Fung ET, Chan DW (2005) Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res 64:5882–5890
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Davis, M.T., Patterson, S.D. (2007). Does the Serum Peptidome Reveal Hemostatic Dysregulation?. In: Bringmann, P., Butcher, E.C., Parry, G., Weiss, B. (eds) Systems Biology. Ernst Schering Research Foundation Workshop, vol 61. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-31339-7_2
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DOI: https://doi.org/10.1007/978-3-540-31339-7_2
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