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

BMC Cancer

Research Article

Jose Cesar Rosa¹  Marcela Gimenez¹  Clarice Izumi¹  Miyuki Uno²  Sueli Oba-Shinjo²  Suely Kazue Nagahashi Marie³  João Bosco Oliveira⁴ 

[1] 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;Department of Neurology, São Paulo Medical School, University of Sao Paulo, Av. Bandeirantes, 3900-14049-900, Ribeirão Preto, São Paulo, Brazil;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;Instituto de Medicina Integral Prof. Fernando Figueira-IMIP, Pernambuco, Brazil;

关键词: Glioma;    Network analysis;    Isobaric tag;    Cancer proteomics;    Biomarkers;   

DOI  :  10.1186/s12885-015-1473-9

 received in 2014-12-05, accepted in 2015-05-26,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundGliomas 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.MethodsiTRAQ-based quantitative proteomic analysis was performed on non-neoplastic brain tissue, on astrocytoma grade II, glioblastoma with short and long survival and oligodendrogliomas.ResultsWe 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.ConclusionTaken 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.

【 授权许可】

Unknown   
© Gimenez et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.