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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: BMC CANCER; v. 15, JUN 25 2015.
• Web of Science Citations: 18

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. 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)

• FAPESP's process: 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine
• Grantee: Berenice Bilharinho de Mendonça
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/07568-7 - Shotgun proteomics in studies of glioma, the interactions of protein complexes with nucleophosmin and proteome/phosphoproteome of glioblastoma multiforme (GBM) derived cell lines stimulated by EGF
• Grantee: José César Rosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system
• Grantee: Suely Kazue Nagahashi Marie
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/06315-3 - The role of microglia activation in human astrocytoma
• Grantee: Suely Kazue Nagahashi Marie
• Support Opportunities: Regular Research Grants