Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1473-9) contains supplementary material, which is available to authorized users.
Highlights
Gliomas account for more than 60 % of all primary central nervous system neoplasms
The tumors were graded as AST Oligodendrogliomas grade II (II) astrocytoma grade II (AST II), glioblastomas (GBM) and oligodendrogliomas grade II (OLI II) and oligodendrogliomas grade Oligodendrogliomas grade III (III) (OLI III)
Non-neoplastic brain tissues (NN, mean age at surgery, 29 ± 7 years, n = 4) were obtained from individuals submitted to temporal lobe resection for epilepsy surgery and examined by a pathologist who confirmed the abundance of astrocytic cells in the resected tissue
Summary
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 main study design concerning GBM has aimed to uncover specific drugable targets in signaling pathways with impact in the tumorigenic process and in the extension of overall survival time [3]. In this context, we have recently described two proteins, nucleophosmin (NPM1) and RKIP, involved in RAS/ RAF/MAPK and PI3K/AKT/mTOR pathways [4]. In the present study we have compared the protein expression profiles of GBM cases presenting short and long survival time, and astrocytoma and oligodendroglioma of different grades of malignancy to further understand the mechanisms of tumor aggressiveness
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