Identification of apolipoprotein A-II in cerebrospinal fluid of pediatric brain tumor patients by protein expression profiling

Judith M de Bont, Monique L den Boer, Roel E Reddingius, Jaap Jansen, Monique Passier, Ron H N van Schaik, Johan M Kros, Peter A E Sillevis Smitt, Theo H Luider, Rob Pieters

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


BACKGROUND: Our aim was to detect differences in protein expression profiles of cerebrospinal fluid (CSF) from pediatric patients with and without brain tumors.

METHODS: We used surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry and Q10 ProteinChip arrays to compare protein expression profiles of CSF from 32 pediatric brain tumor patients and 70 pediatric control patients. A protein with high discriminatory power was isolated and identified by subsequent anion-exchange and reversed-phase fractionation, gel electrophoresis, and mass spectrometry. The identity of the protein was confirmed by Western blotting and immunohistochemistry.

RESULTS: Of the 247 detected protein peak clusters, 123 were differentially expressed between brain tumor and control patients with a false discovery rate of 1%. Double-loop classification analysis gave a mean prediction accuracy of 88% in discriminating brain tumor patients from control patients. From the 123 clusters, a highly overexpressed protein peak cluster in CSF from brain tumor patients was selected for further analysis and identified as apolipoprotein A-II. Apolipoprotein A-II expression in CSF was correlated with the CSF albumin concentration, suggesting that the overexpression of apolipoprotein A-II is related to a disrupted blood-brain barrier.

CONCLUSIONS: SELDI-TOF mass spectrometry can be successfully used to find differentially expressed proteins in CSF of pediatric brain tumor and control patients. Apolipoprotein A-II is highly overexpressed in CSF of pediatric brain tumor patients, which most likely is related to a disrupted blood-brain barrier. Ongoing studies are aimed at finding subtype specific proteins in larger groups of pediatric brain tumor patients.

Original languageEnglish
Pages (from-to)1501-9
Number of pages9
JournalClinical chemistry
Issue number8
Publication statusPublished - Aug 2006
Externally publishedYes


  • Apolipoprotein A-II/cerebrospinal fluid
  • Biomarkers, Tumor/cerebrospinal fluid
  • Blood-Brain Barrier
  • Brain Neoplasms/cerebrospinal fluid
  • Child
  • Female
  • Humans
  • Male
  • Proteome/biosynthesis
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods


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