Protein profiling as a diagnostic tool in clinical chemistry: a review

Judith A. P. Bons 1. , 1. , Will K. W. H. Wodzig 2. , 2. ,  and Marja P. van Dieijen-Visser 3. , 3.
  • 1. Department of Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands
  • 2. Department of Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands
  • 3. Department of Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands


Serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) appears to be an important diagnostic tool for a whole range of diseases. Sensitivities and specificities obtained with this new technology often seem superior to those obtained with current biomarkers. However, reproducibility and standardization are still problematic. The present review gives an overview of the diagnostic value of protein profiles obtained with SELDI in studies on prostate and ovarian cancer. To identify aspects important for protein profiling, we compare and discuss differences in pre- and post-analytical conditions presented in the literature supplemented with some of our own data. Further progress in protein profiling as a diagnostic tool requires a more comprehensive description of technical details in all future studies.

  • 1.

    Hutchens TW, Yip T. New desorption strategies for the mass spectrometric analysis of macromolecules. Rapid Commun Mass Spectrom 1993; 7:576–80.

  • 2.

    Petricoin I, Emanuel F, Mills GB, Kohn EC, Liotta LA. Proteomic patterns in serum and identification of ovarian cancer. Lancet 2002; 360:170–1.

  • 3.

    Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 2002; 359:572–7.

  • 4.

    Kozak KR, Amneus MW, Pusey SM, Su F, Luong MN, Luong SA, et al. Identification of biomarkers for ovarian cancer using strong anion-exchange ProteinChips: potential use in diagnosis and prognosis. Proc Natl Acad Sci USA 2003; 100:12343–8.

  • 5.

    Zhang Z, Bast RC Jr, Yu Y, Li J, Sokoll LJ, Rai AJ, et al. Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res 2004; 64:5882–90.

  • 6.

    Vlahou A, Schorge JO, Gregory BW, Coleman RL. Diagnosis of ovarian cancer using decision tree classification of mass spectral data. J Biomed Biotechnol 2003; 2003:308–14.

  • 7.

    Ye B, Cramer DW, Skates SJ, Gygi SP, Pratomo V, Fu L, et al. Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry. Clin Cancer Res 2003; 9:2904–11.

  • 8.

    Rai AJ, Zhang Z, Rosenzweig J, Shih IM, Pham T, Fung ET, et al. Proteomic approaches to tumor marker discovery. Arch Pathol Lab Med 2002; 126:1518–26.

  • 9.

    Banez LL, Prasanna P, Sun L, Ali A, Zou Z, Adam BL, et al. Diagnostic potential of serum proteomic patterns in prostate cancer. J Urol 2003; 170:442–6.

  • 10.

    Adam BL, Qu Y, Davis JW, Ward MD, Clements MA, Cazares LH, et al. Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. Cancer Res 2002; 62:3609–14.

  • 11.

    Petricoin EF III, Ornstein DK, Paweletz CP, Ardekani A, Hackett PS, Hitt BA, et al. Serum proteomic patterns for detection of prostate cancer. J Natl Cancer Inst 2002; 94:1576–8.

  • 12.

    Qu Y, Adam BL, Yasui Y, Ward MD, Cazares LH, Schellhammer PF, et al. Boosted decision tree analysis of surface-enhanced laser desorption/ionization mass spectral serum profiles discriminates prostate cancer from noncancer patients. Clin Chem 2002; 48:1835–43.

  • 13.

    Li J, White N, Zhang Z, Rosenzweig J, Mangold LA, Partin AW, et al. Detection of prostate cancer using serum proteomics pattern in a histologically confirmed population. J Urol 2004; 171:1782–7.

  • 14.

    Zhukov TA, Johanson RA, Cantor AB, Clark RA, Tockman MS. Discovery of distinct protein profiles specific for lung tumors and pre-malignant lung lesions by SELDI mass spectrometry. Lung Cancer 2003; 40:267–79.

  • 15.

    Poon TC, Hui AY, Chan HL, Ang IL, Chow SM, Wong N, et al. Prediction of liver fibrosis and cirrhosis in chronic hepatitis B infection by serum proteomic fingerprinting: a pilot study. Clin Chem 2004; 51:328–35.

  • 16.

    Zhu XD, Zhang WH, Li CL, Xu Y, Liang WJ, Tien P. New serum biomarkers for detection of HBV-induced liver cirrhosis using SELDI protein chip technology. World J Gastroenterol 2004; 10:2327–9.

  • 17.

    Wiesner A. Detection of tumor markers with ProteinChip technology. Curr Pharm Biotechnol 2004; 5:45–67.

  • 18.

    Diamandis EP. How are we going to discover new cancer biomarkers? A proteomic approach for bladder cancer. Clin Chem 2004; 50:793–5.

  • 19.

    Xiao Z, Prieto D, Conrads TP, Veenstra TD, Issaq HJ. Proteomic patterns: their potential for disease diagnosis. Mol Cell Endocrinol 2005; 230:95–106.

  • 20.

    Belenky A, Smith A, Zhang B, Lin S, Despres N, Wu AH, et al. The effect of class-specific protease inhibitors on the stabilization of B-type natriuretic peptide in human plasma. Clin Chim Acta 2004; 340:163–72.

  • 21.

    WHO document “Use of anticoagulants in diagnostic laboratory investigations” (WHO/DIL/LAB/99.1 Rev. 2).

  • 22.

    Solassol J, Marin P, Demettre E, Rouanet P, Bockaert J, Maudelonde T, et al. Proteomic detection of prostate-specific antigen using a serum fractionation procedure: potential implication for new low-abundance cancer biomarkers detection. Anal Biochem 2005; 338:26–31.

  • 23.

    Linke T, Ross AC, Harrison EH. Profiling of rat plasma by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, a novel tool for biomarker discovery in nutrition research. J Chromatogr A 2004; 1043:65–71.

  • 24.

    Baggerly KA, Morris JS, Coombes KR. Cautions about reproducibility in mass spectrometry patterns: joint analysis of several proteomic data sets., 2003.

  • 25.

    Malik G, Ward MD, Gupta SK, Trosset MW, Grizzle WE, Adam BL, et al. Serum levels of an isoform of apolipoprotein A-II as a potential marker for prostate cancer. Clin Cancer Res 2005; 11:1073–85.

  • 26.

    Wright GL Jr, Cazares LH, Leung SM, Nasim S, Adam BL, Yip TT, et al. Proteinchip(R) surface enhanced laser desorption/ionization (SELDI) mass spectrometry: a novel protein biochip technology for detection of prostate cancer biomarkers in complex protein mixtures. Prostate Cancer Prostatic Dis 1999; 2:264–76.

  • 27.

    Xiao Z, Adam BL, Cazares LH, Clements MA, Davis JW, Schellhammer PF, et al. Quantitation of serum prostate-specific membrane antigen by a novel protein biochip immunoassay discriminates benign from malignant prostate disease. Cancer Res 2001; 61:6029–33.

  • 28.

    Semmes OJ, Feng Z, Adam BL, Banez LL, Bigbee WL, Campos D, et al. Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility. Clin Chem 2005; 51:102–12.

  • 29.

    Lee SW, Lee KI, Kim JY. Revealing urologic diseases by proteomic techniques. J Chromatogr B 2005; 815:203–13.

  • 30.

    Orchard S, Zhu W, Julian RK Jr, Hermjakob H, Apweiler R. Further advances in the development of a data interchange standard for proteomics data. Proteomics 2003; 3:2065–6.

  • 31.

    Orchard S, Hermjakob H, Apweiler R. The proteomics standards initiative. Proteomics 2003; 3:1374–6.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.