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

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.

AS1411-Induced Growth Inhibition of Glioma Cells by Up-Regulation of p53 and Down-Regulation of Bcl-2 and Akt1 via Nucleolin

“…Most importantly, AS1411 inhibited the growth of mouse glioma xenograft and prolonged the survival time of glioma tumor-bearing mice. Furthermore, targeting NCL means AS1411 may induce a stronger curative effect on high grade glioma which expresses higher level of NCL [19, 54]. In all, our results suggest a promising further development of AS1411 for the treatment of glioma patients in clinic.…”

Tumour cell dormancy as a contributor to the reduced survival of GBM patients who received standard therapy

“…HSPB1 (also known as HP27) encodes heat shock protein family B member 1, which functions as a molecular chaperone, probably maintaining denatured proteins in a folding-competent state. Recently, HSPB1 was proposed to be a discriminating short protein that is a long survival factor in GBM (42). HSP27 mediates SPARC-induced changes in glioma morphology and invasion (43), and inhibition of HSP27 alone or in combination with pAKT inhibition may be an effective therapeutic approach (44).…”

Downregulation of antigen presentation-associated pathway proteins is linked to poor outcome in triple-negative breast cancer patient tumors

“…4, Network 2). The heat shock protein HSPB1, a known factor involved in preventing apoptosis 44 and tumor progression, 45 was found to interact with both major key nodes in Network 2 and elevated recurrence versus recurrencefree patients (1.4-fold)( Fig. 4, Network 2).…”