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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Gimenez, Marcela [1, 2] ; Nagahashi Marie, Suely Kazue [3, 4] ; Oba-Shinjo, Sueli [3] ; Uno, Miyuki [3] ; Izumi, Clarice [1, 2] ; Oliveira, Joao Bosco [5] ; Rosa, Jose Cesar [1, 2]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Mol & Cell Biol, Sao Paulo - Brazil
[2] Univ Sao Paulo, CEPID FAPESP Hemoctr Ribeiro Preto, Prot Chem Ctr, CTC Ctr Cell Therapy, Ribeirao Preto Med Sch, Sao Paulo - Brazil
[3] Univ Sao Paulo, Sao Paulo Med Sch, Dept Neurol, BR-14049900 Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Ctr Studies Cellular & Mol Therapy NETCEM, Sao Paulo - Brazil
[5] Inst Med Integral Prof Fernando Figueira IMIP, Pernambuco - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: BMC CANCER; v. 15, JUN 25 2015.
Citações Web of Science: 18
Resumo

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. Conclusion: 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. (AU)

Processo FAPESP: 11/07568-7 - Shotgun proteomics em estudos de glioma, nas interações de complexos protéicos com nucleofosmina e no proteoma/fosfoproteoma de linhagens celulares derivadas de glioblastoma multiforme (GBM) estimuladas por EGF
Beneficiário:José César Rosa
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 01/00422-5 - Estudo das mutações no gene alpha-glucosidade ácida (GAA) na glicogenose tipo II (GS II)
Beneficiário:Suely Kazue Nagahashi Marie
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/06315-3 - Papel da ativação da micróglia em astrocitomas humanos
Beneficiário:Suely Kazue Nagahashi Marie
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/02162-8 - Patogênese molecular e caracterização de doenças monogênicas do desenvolvimento: um caminho para a medicina translacional
Beneficiário:Berenice Bilharinho de Mendonça
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
Beneficiário:Suely Kazue Nagahashi Marie
Linha de fomento: Auxílio à Pesquisa - Temático