title: Molecular classification and survival prediction in human gliomas based on proteome analysis.
abstract: The biological features of gliomas, which are characterized by highly heterogeneous biological aggressiveness even in the same histological category, would be precisely described by global gene expression data at the protein level. We investigated whether proteome analysis based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can identify differences in protein expression between high- and low-grade glioma tissues. Proteome profiling patterns were compared in 85 tissue samples: 52 glioblastoma multiforme, 13 anaplastic astrocytomas, 10 atrocytomas, and 10 normal brain tissues. We could completely distinguish the normal brain tissues from glioma tissues by cluster analysis based on the proteome profiling patterns. Proteome-based clustering significantly correlated with the patient survival, and we could identify a biologically distinct subset of astrocytomas with aggressive nature. Discriminant analysis extracted a set of 37 proteins differentially expressed based on histological grading. Among them, many of the proteins that were increased in high-grade gliomas were categorized as signal transduction proteins, including small G-proteins. Immunohistochemical analysis confirmed the expression of identified proteins in glioma tissues. The present study shows that proteome analysis is useful to develop a novel system for the prediction of biological aggressiveness of gliomas. The proteins identified here could be novel biomarkers for survival prediction and rational targets for antiglioma therapy.
authors.affiliation: Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan. iwadate@med.m.chiba-u.ac.jp
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwadate
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakaida
authors.forename: Takaki
authors.initials: T
authors.lastname: Hiwasa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nagai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikura
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaura
mesh_terms: D000595:Amino Acid Sequence; D001932:Brain Neoplasms / Q000378:metabolism*; D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome