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.
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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DOI：
10.1186/s12885-015-1473-9
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发表时间：
2015-06-25
期刊：
影响因子：
3.8
通讯作者：
Rosa JC
中科院分区：
文献类型：
--
作者：
Gimenez M;Marie SK;Oba-Shinjo S;Uno M;Izumi C;Oliveira JB;Rosa JC
胶质瘤占所有原发性中枢神经系统肿瘤的60%以上。低级别胶质瘤表现出向更恶性表型发展的趋势，最常见和最恶性的胶质母细胞瘤(GBM)。另一种类型的胶质瘤是少突胶质细胞瘤，起源于少突胶质细胞和胶质前体细胞，占胶质瘤的2%-5%。这两种类型的胶质瘤之间的区别实际上是有争议的，因此，为了更好地诊断，分子区分是必要的。对非肿瘤性脑组织、II级星形细胞瘤、生存期短、长的胶质母细胞瘤和少突胶质细胞瘤进行了iTRAQ定量蛋白质组学分析。我们发现，在胶质母细胞瘤中，核磷蛋白(NPM1)、葡萄糖调节蛋白78 kDa(GRP78)、核仁素(NCL)和热休克蛋白90 kDa(HSP90B1)的表达增加，Raf激酶抑制蛋白(RKIP/PEBP1)的表达减少，它们与肿瘤进展相关的网络有关。热休克蛋白27(HSPB 1/HSP27)的表达水平区分了胶质母细胞瘤的短生存期(6 ± 4个月，n = 4)和长生存期(43 ± 15个月，n = 4)(p = 0.00045)。在低级别少突胶质细胞瘤和II级星形细胞瘤中，NOVA1的表达水平差异有统计学意义(p = 0.0082)。通过Western印迹、qRT-PCR和免疫组织化学在较大的病例中进行验证。总之，我们的定量蛋白质组分析检测到与肿瘤进展相关的网络中的分子三联体、NPM1、GRP78和RKIP与NCL和HSP27/HSPB1一起参与。此外，还发现了两个新的重要靶点：NOVA1有助于星形细胞瘤和少突胶质细胞瘤的诊断和鉴别；HSPB1/HSP27是GBM预后不良的预测因子。本文的在线版本(doi：10.1186/s12885-0151473-9)包含补充材料，授权用户可以使用。
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. iTRAQ-based quantitative proteomic analysis was performed on non-neoplastic brain tissue, on astrocytoma grade II, glioblastoma with short and long survival and oligodendrogliomas. 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. 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. The online version of this article (doi:10.1186/s12885-015-1473-9) contains supplementary material, which is available to authorized users.