title: Quantitative proteomic analysis shows differentially expressed HSPB1 in glioblastoma as a discriminating short from long survival factor and NOVA1 as a differentiation factor between low-grade astrocytoma and oligodendroglioma.
abstract: BACKGROUND
  Gliomas account for more than 60 % of all primary central nervous system neoplasms. Low-grade gliomas display a tendency to progress to more malignant phenotypes and the most frequent and malignant gliomas are glioblastomas (GBM). Another type of glioma, oligodendroglioma originates from oligodendrocytes and glial precursor cells and represents 2-5 % of gliomas. The discrimination between these two types of glioma is actually controversial, thus, a molecular distinction is necessary for better diagnosis.
  
  
  METHODS
  iTRAQ-based quantitative proteomic analysis was performed on non-neoplastic brain tissue, on astrocytoma grade II, glioblastoma with short and long survival and oligodendrogliomas.
  
  
  RESULTS
  We found that expression of nucleophosmin (NPM1), glucose regulated protein 78 kDa (GRP78), nucleolin (NCL) and heat shock protein 90 kDa (HSP90B1) were increased, Raf kinase inhibitor protein (RKIP/PEBP1) was decreased in glioblastoma and they were associated with a network related to tumor progression. Expression level of heat shock protein 27 (HSPB1/HSP27) discriminated glioblastoma presenting short (6 ± 4 months, n = 4) and long survival (43 ± 15 months, n = 4) (p = 0.00045). Expression level of RNA binding protein nova 1 (NOVA1) differentiated low-grade oligodendroglioma and astrocytoma grade II (p = 0.0082). Validation were done by Western blot, qRT-PCR and immunohistochemistry in a larger casuistry.
  
  
  CONCLUSIONS
  Taken together, our quantitative proteomic analysis detected the molecular triad, NPM1, GRP78 and RKIP participating together with NCL and HSP27/HSPB1 in a network related to tumor progression. Additionally, two new important targets were uncovered: NOVA1 useful for diagnostic refinement differentiating astrocytoma from oligodendroglioma, and HSPB1/HSP27, as a predictive factor of poor prognosis for GBM.
authors.affiliation: Department Molecular and Cell Biology and Protein Chemistry Center, CTC-Center for Cell Therapy-CEPID-FAPESP-Hemocentro de Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Gimenez
authors.affiliation: Department of Neurology, São Paulo Medical School, University of Sao Paulo, Av. Bandeirantes, 3900-14049-900, Ribeirão Preto, São Paulo, Brazil.|Center for Studies of Cellular and Molecular Therapy (NETCEM) University of Sao Paulo, São Paulo, Brazil.
authors.forename: Suely Kazue Nagahashi
authors.initials: SK
authors.lastname: Marie
authors.affiliation: Department of Neurology, São Paulo Medical School, University of Sao Paulo, Av. Bandeirantes, 3900-14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Sueli
authors.initials: S
authors.lastname: Oba-Shinjo
authors.affiliation: Department of Neurology, São Paulo Medical School, University of Sao Paulo, Av. Bandeirantes, 3900-14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Uno
authors.affiliation: Department Molecular and Cell Biology and Protein Chemistry Center, CTC-Center for Cell Therapy-CEPID-FAPESP-Hemocentro de Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Clarice
authors.initials: C
authors.lastname: Izumi
authors.affiliation: Instituto de Medicina Integral Prof. Fernando Figueira-IMIP, Pernambuco, Brazil.
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Oliveira
authors.affiliation: Department Molecular and Cell Biology and Protein Chemistry Center, CTC-Center for Cell Therapy-CEPID-FAPESP-Hemocentro de Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. jcrosa@fmrp.usp.br.
authors.forename: Jose Cesar
authors.initials: JC
authors.lastname: Rosa
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis* / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D007553:Isotope Labeling; D008875:Middle Aged; D018832:Molecular Chaperones; D000090682:Neuro-Oncological Ventral Antigen; D000090243:Nucleophosmin; D009837:Oligodendroglioma / Q000378:metabolism* / Q000401:mortality; D011237:Predictive Value of Tests; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics; D016601:RNA-Binding Proteins / Q000032:analysis* / Q000378:metabolism; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D055551:HSP27 Heat-Shock Proteins; C000717247:HSPA5 protein, human; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C000594513:NOVA1 protein, human; C000716967:NPM1 protein, human; D000090682:Neuro-Oncological Ventral Antigen; D020543:Proteome; D016601:RNA-Binding Proteins; D000090243:Nucleophosmin