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Assessment of protein stability in cerebrospinal fluid using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein profiling

Abstract

Recent studies have evaluated proper acquisition and storage procedures for the use of serum or plasma for mass spectrometry (MS)-based proteomics. The present study examines the proteome stability of human cerebrospinal fluid (CSF) over time at 23°C (room temperature) and 4°C using surface-enhanced laser desorption/ionization time-of-flight MS. Data analysis revealed that statistically significant differences in protein profiles are apparent within 4 h at 23°C and between 6 and 8 h at 4°C. Inclusion of protease and phosphatase inhibitor cocktails into the CSF samples failed to significantly reduce proteome alterations over time. We conclude that MS-based proteomic analysis of CSF requires careful assessment of sample collection procedures for rapid and optimal sample acquisition and storage.

References

  1. Petricoln, E. F., Ardekani, A. M., Hitt, B. A., et al. (2002) Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359, 572–577.

    Article  Google Scholar 

  2. Rosty, C., Christa, L., Kuzdzal, S., et al. (2002) Identification of hepatocarcinoma-intestine-pancreas/ pancreatitis-associated protein I as a biomarker for pancreatic ductal adenocarcinoma by protein biochip technology. J. Cancer Res. 62, 1868–1875.

    CAS  Google Scholar 

  3. Rogers, M. A., Clarke, P., Noble, J., et al. (2003) Proteomic profiling of urinary proteins in renal cancer by surface enhanced laser desorption Ionization and neural-network analysis: Identification of key issues affecting potential clinical utility. Cancer Res. 63, 6971–6983.

    PubMed  CAS  Google Scholar 

  4. Carrette, O., Demalte, I., Scherl, A., et al. (2003) A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer's disease. Proteomics 3, 1486–1494.

    Article  PubMed  CAS  Google Scholar 

  5. Xiao, Z., Luke, B. T., Izmirlian, G., et al. (2004) Serum proteomic profiles suggest celecoxib-modulated targets and response predictors. Cancer Res. 64, 2904–2909.

    Article  PubMed  CAS  Google Scholar 

  6. Kozak, K. R., Su, F., Whitelegge, J. P., Faull, K., Reddy, S., and Farias-Eisner, R. (2005) Characterization of serum biomarkers for detection of early stage ovarian cancer. Proteomics 5, 4589–4596.

    Article  PubMed  CAS  Google Scholar 

  7. Norwitz, E. R., Tsen, L. C., Park, J. S., et al. (2005) Discriminatory proteomic biomarker analysis identifies free hemoglobin in the cerebrospinal fluid of women with severe preeclampsia. Am. J. Obstet. Gynecol. 193, 957–964.

    Article  PubMed  CAS  Google Scholar 

  8. Woodrum, D., French, C., and Shamel, L. B. (1996) Stability of free prostate-specific antigen in serum samples under a variety of sample collection and sample storage conditions. Urology 48, 33–39.

    Article  PubMed  CAS  Google Scholar 

  9. Raabe, A., Kopetsch, O., Gross, U., Zimmermann, M., and Gebhart, P. (2003) Measurements of serum S-100B protein: effects of storage time and temperature on pre-analytical stability. Clin. Chem. Lab. Med. 41, 700–703.

    Article  PubMed  CAS  Google Scholar 

  10. Delatour, T. (2004) Performance of quantitative analyses by liquid chromatography-electrospray ionisation tandem mass spectrometry: from external calibration to isotopomer-based exact matching. Anal. Bioanal. Chem. 380, 515–523.

    Article  PubMed  CAS  Google Scholar 

  11. Spruessel, A., Steimann, G., Jung, M., et al. (2004) Tissue ischemia time affects gene and protein expression patterns within minutes following surgical tumor excision. Biotechniques 36, 1030–1037.

    PubMed  CAS  Google Scholar 

  12. West-Nielsen, M., Hogdall, E. V., Marchiori, E., Hogdall, C. K., Schou, C., and Heegaard, N. H. H. (2005) Sample handling for mass spectrometric proteomic investigations of human sera. Anal. Chem. 77, 5114–5123.

    Article  PubMed  CAS  Google Scholar 

  13. Hesse, C., Larsson, H., Fredman, P., et al. (2000) Measurement of apolipoprotein E (apoE) in cerebrospinal fluid. Neurochem. Res. 25, 511–517.

    Article  PubMed  CAS  Google Scholar 

  14. Semmes, O. J., Feng, Z., Adam, B.-L., et al. (2005) 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. 51, 102–112.

    Article  PubMed  CAS  Google Scholar 

  15. Carrette, O., Burkhard, P. R., Hughes, S., Hochstrasser, D. F., and Sanchez, J. C. (2005) Truncated cystatin C in cerebrospinal fluid: technical artefact or biological process? Proteomics 5, 3060–3065.

    Article  PubMed  CAS  Google Scholar 

  16. Yuan, X., Russell, T., Wood, G., and Desiderio, D. M. (2002) Analysis of the human lumbar cerebrospinal fluid proteome. Electrophoresis 23, 1185–1196.

    Article  PubMed  CAS  Google Scholar 

  17. Davidsson, P., Sjogren, M., Andreasen, N., et al. (2002) Studies of the pathophysiological mechanisms of frontotemporal dementia by proteome analysis of CSF proteins. Mol. Brain Res. 109, 128–133.

    Article  PubMed  CAS  Google Scholar 

  18. Ramstrom, M., Ivonin, I., Johansson, A., et al. (2005) Cerebrospinal fluid protein patterns in neurodegenerative disease revealed by liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. Proteomics 4, 4010–4018.

    Article  Google Scholar 

  19. Levine, J., Panchalingam, K., McClure, R. J., Gershon, S., and Pettegrew, J. W. (2000) Stability of CSF metabolites measured by proton NMR. J. Neural Transm. 107, 843–848.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang, J., Goodlett, D. R., Peskind, E. R., et al. (2005) Quantitative proteomic analysis of age-related changes in human cerebrospinal fluid. Neurobiol. Aging 26, 207–227.

    Article  PubMed  CAS  Google Scholar 

  21. Maccarrone, G., Birg, I., Malisch, E., et al. (2004) In-depth analysis of the human CSF proteome using protein prefractionation. Clin. Proteomics 1, 333–364.

    Article  CAS  Google Scholar 

  22. Hulmes, J. D., Bethea, D., Ho, K., et al. (2004) An investigation of plasma collection, stabilization, and storage procedures for proteomic analysis of clinical samples. Clin. Proteomics 1(1), 17–31.

    Article  CAS  Google Scholar 

  23. Marshall, J., Kupchak, P., Zhu, W., et al. (2003) Processing of serum proteins underlies the mass spectral fingerprinting of myocardial infarction. J. Proteome Res. 2, 361–372.

    Article  PubMed  CAS  Google Scholar 

  24. You, J.-S., Gelfanova, V., Knierman, M. D., Witzmann, F. A., Wang, M., and Hale, J. E. (2005) The impact of blood contamination on the proteome of cerebrospinal fluid. Proteomics 5, 290–296.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Robert Bowser.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Ranganathan, S., Polshyna, A., Nicholl, G. et al. Assessment of protein stability in cerebrospinal fluid using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein profiling. Clin Proteom 2, 91–101 (2006). https://doi.org/10.1385/CP:2:1:91

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