title: Proteomic identification of biomarkers in the cerebrospinal fluid (CSF) of astrocytoma patients.
abstract: The monitoring of changes in the protein composition of the cerebrospinal fluid (CSF) can be used as a sensitive indicator of central nervous system (CNS) pathology, yet its systematic application to analysis of CNS neoplasia has been limited. There is a pressing need for both a better understanding of gliomagenesis and the development of reliable biomarkers of the disease. In this report, we used two proteomic techniques, two-dimensional gel electrophoresis (2-DE), and cleavable Isotope-Coded Affinity Tag (cICAT) to compare CSF proteomes to identify tumor- and grade-specific biomarkers in patients bearing brain tumors of differing histologies and grades. Retrospective analyses were performed on 60 samples derived from astrocytomas WHO grade II, III, and IV, schwannomas, metastastic brain tumors, inflammatory samples, and non-neoplastic controls. We identified 103 potential tumor-specific markers of which 20 were high-grade astrocytoma-specific. These investigations allowed us to identify a spectrum of signature proteins that could be used to distinguish CSF derived from control patients versus those with low- (AII) or high-grade (AIV) astrocytoma. These proteins may represent new diagnostic, prognostic, and disease follow-up markers when used alone or in combination. These candidate biomarkers may also have functional properties that play a critical role in the development and malignant progression of human astrocytomas, thus possibly representing novel therapeutic targets for this highly lethal disease.
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery and Winship Cancer Institute, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322, USA.
authors.forename: Fatima W
authors.initials: FW
authors.lastname: Khwaja
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Reed
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Schmotzer
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.forename: Abhijit
authors.initials: A
authors.lastname: Guha
authors.forename: Morris D
authors.initials: MD
authors.lastname: Groves
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.forename: Jan
authors.initials: J
authors.lastname: Pohl
authors.forename: Erwin G
authors.initials: EG
authors.lastname: Van Meir
mesh_terms: D000345:Affinity Labels; D001254:Astrocytoma / Q000134:cerebrospinal fluid*; D014408:Biomarkers, Tumor / Q000032:analysis; D005910:Glioma / Q000134:cerebrospinal fluid; D006801:Humans; D009363:Neoplasm Proteins / Q000134:cerebrospinal fluid*; D020543:Proteome / Q000302:isolation & purification*; D012680:Sensitivity and Specificity
chemical_list: D000345:Affinity Labels; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome