Proteomic profiling of cerebrospinal fluid identifies prostaglandin D2 synthase as a putative biomarker for pediatric medulloblastoma: A pediatric brain tumor consortium study

Proteomics. 2011 Mar;11(5):935-43. doi: 10.1002/pmic.201000198. Epub 2011 Jan 27.

Abstract

The aims of this study were to demonstrate the feasibility of centrally collecting and processing high-quality cerebrospinal fluid (CSF) samples for proteomic studies within a multi-center consortium and to identify putative biomarkers for medulloblastoma in CSF. We used 2-DE to investigate the CSF proteome from 33 children with medulloblastoma and compared it against the CSF proteome from 25 age-matched controls. Protein spots were subsequently identified by a combination of in-gel tryptic digestion and MALDI-TOF TOF MS analysis. On average, 160 protein spots were detected by 2-DE and 76 protein spots corresponding to 25 unique proteins were identified using MALDI-TOF. Levels of prostaglandin D2 synthase (PGD2S) were found to be six-fold decreased in the tumor samples versus control samples (p<0.00001). These data were further validated using ELISA. Close examination of PGD2S spots revealed the presence of complex sialylated carbohydrates at residues Asn(78) and Asn(87) . Total PGD2S levels are reduced six-fold in the CSF of children with medulloblastoma most likely representing a host response to the presence of the tumor. In addition, our results demonstrate the feasibility of performing proteomic studies on CSF samples collected from patients at multiple institutions within the consortium setting.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Asparagine / metabolism
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism*
  • Brain Neoplasms / cerebrospinal fluid
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / genetics
  • Carbohydrate Sequence
  • Case-Control Studies
  • Child
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Profiling*
  • Humans
  • Intramolecular Oxidoreductases / cerebrospinal fluid
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism*
  • Lipocalins / cerebrospinal fluid
  • Lipocalins / genetics
  • Lipocalins / metabolism*
  • Medulloblastoma / cerebrospinal fluid
  • Medulloblastoma / diagnosis
  • Medulloblastoma / enzymology*
  • Medulloblastoma / genetics
  • Molecular Sequence Data
  • Pediatrics
  • Protein Isoforms / cerebrospinal fluid
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Proteome / analysis
  • Proteomics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Trypsin / metabolism

Substances

  • Biomarkers
  • Lipocalins
  • Protein Isoforms
  • Proteome
  • Asparagine
  • Trypsin
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase