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Search for Breast Cancer Biomarkers in Fractionated Serum Samples by Protein Profiling With SELDI-TOF MS

  1. Annemieke W.J. Opstal-van Winden1,2,
  2. Jos H. Beijnen2,3,
  3. Arnoud Loof4,
  4. Waander L. van Heerde4,
  5. Roel Vermeulen1,5,
  6. Petra H.M. Peeters1,6,
  7. Carla H. van Gils1,*

Article first published online: 24 JAN 2012

DOI: 10.1002/jcla.20492

Issue

Journal of Clinical Laboratory Analysis

Journal of Clinical Laboratory Analysis

Volume 26, Issue 1, pages 1–9, January 2012

Additional Information

How to Cite

Opstal-van Winden, A. W.J., Beijnen, J. H., Loof, A., van Heerde, W. L., Vermeulen, R., Peeters, P. H.M. and van Gils, C. H. (2012), Search for Breast Cancer Biomarkers in Fractionated Serum Samples by Protein Profiling With SELDI-TOF MS. J. Clin. Lab. Anal., 26: 1–9. doi: 10.1002/jcla.20492

Author Information

  1. 1

    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

  2. 2

    Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

  3. 3

    Beta Faculty, Department of Pharmaceutical Sciences, Division of Biomedical Analysis, Section of Drug Toxicology, Utrecht University, Utrecht, The Netherlands

  4. 4

    Central Laboratory for Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

  5. 5

    Institute for Risk Assessment Sciences, Utrecht University, The Netherlands

  6. 6

    Department of Epidemiology, Public Health and Primary Care, Faculty of Medicine, Imperial College, London, United Kingdom

*Correspondence to: Carla H. van Gils, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Mail-drop Str 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.

Publication History

  1. Issue published online: 24 JAN 2012
  2. Article first published online: 24 JAN 2012
  3. Manuscript Accepted: 31 AUG 2011
  4. Manuscript Received: 20 JUL 2011

Funded by

  • University Medical Center Utrecht; Julius Center for Health Sciences and Primary Care

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Keywords:

  • breast cancer;
  • proteomics;
  • SELDI-TOF MS;
  • fractionation;
  • biomarker

Background

Many high-abundant acute phase reactants have been previously detected as potential breast cancer biomar-kers. However, they are unlikely to be specific for breast cancer. Cancer-specific biomarkers are thought to be among the lower abundant proteins.

Methods

We aimed to detect lower abundant discriminating proteins by performing serum fractionation by strong anion exchange chromatography preceding protein profiling with SELDI-TOF MS. In a pilot study, we tested the different fractions resulting from fractionation, on several array types. Fraction 3 on IMAC30 and Fraction 6 on Q10 yielded the most discriminative proteins and were used for serum protein profiling of 73 incident breast cancer cases and 73 matched controls.

Results

Eight peaks showed statistically significantly different intensities between cases and controls (P⧁0.05), and had less than 10% chance to be a false-positive finding. Seven of these were tentatively identified as apolipoprotein C-II (m/z 8,909), oxidized apolipoprotein C-II (m/z 8,925), apolipoprotein C-III (m/z 8,746), fragment of coagulation factor XIIIa (m/z 3,959), heterodimer of apolipoprotein A-I and apolipoprotein A-II (m/z 45,435), hemoglobin B-chain (m/z 15,915), and post-translational modified hemoglobin (m/z 15,346).

Conclusion

By extensive serum fractionation, we detected many more proteins than in previous studies without fractionation. However, discriminating proteins were still high abundant. Results indicate that either lower abundant proteins are less distinctive, or more rigorous fractionation and selective protein depletion, or a more sensitive assay, are needed to detect lower abundant discriminative proteins.

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