title: Proteomic profiling of cerebrospinal fluid identifies prostaglandin D2 synthase as a putative biomarker for pediatric medulloblastoma: A pediatric brain tumor consortium study.
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.
authors.affiliation: Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Meena U
authors.initials: MU
authors.lastname: Rajagopal
authors.forename: Yetrib
authors.initials: Y
authors.lastname: Hathout
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
authors.forename: Sri
authors.initials: S
authors.lastname: Gururangan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Peter
authors.initials: P
authors.lastname: Phillips
authors.forename: Roger
authors.initials: R
authors.lastname: Packer
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.forename: Brian R
authors.initials: BR
authors.lastname: Rood
mesh_terms: D000595:Amino Acid Sequence; D001216:Asparagine / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D002648:Child; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D008527:Medulloblastoma / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D010372:Pediatrics; D020033:Protein Isoforms / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000032:analysis; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014357:Trypsin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D054834:Lipocalins; D020033:Protein Isoforms; D020543:Proteome; D001216:Asparagine; D014357:Trypsin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase