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人类胶质瘤的基因表达谱揭示了胶质母细胞瘤(GBM)和低级别星形细胞瘤(LGA)在能量代谢和Notch信号通路方面的差异。

Gene expression profiling of human gliomas reveals differences between GBM and LGA related to energy metabolism and notch signaling pathways.

作者信息

Margareto Javier, Leis Olatz, Larrarte Eider, Idoate Miguel A, Carrasco Alejandro, Lafuente José Vicente

机构信息

LEIA Foundation, Pharmaceutical Development Unit, Leonardo de Vinci, 11; Alava Technologic Park, 01510 Miñano, Alava, Spain.

出版信息

J Mol Neurosci. 2007;32(1):53-63. doi: 10.1007/s12031-007-0008-5.

Abstract

Human malignant astrocytic tumors are the most common primary brain malignancies. Human gliomas are classified according to the extent of anaplasia or 'de-differentiation' appearance. Although this type of histological classification is widely accepted, the extensive heterogeneity of astrocytic tumors has made their pathological classification rather difficult. New genome-scale high throughput technologies for gene expression profiling, such as DNA microarrays, are emerging as new tools to allow a more accurate identification and characterization of different tumor degrees by discovering new specific markers and pathways of each stage. Present work reports interesting results that might be useful to differentiate between tumor grades. Data presented here provides new evidences about the molecular basis underlying different tumor stages. In this sense, we identified key metabolic pathways, crucial for tumor progression, as being differentially regulated in different tumor stages. On the other hand, remarkable findings regarding Notch pathway are reported, as some members of this receptor family were found to be differentially expressed depending on the malignancy degree. Our results clearly point out important molecular differences between different tumor stages and suggest that more studies are needed to understand specific molecular events characteristic of each stage. These types of studies represent a first step to deepen into the tumor physiology, which may potentially help for better and a more precise diagnosis of gliomas.

摘要

人类恶性星形细胞瘤是最常见的原发性脑恶性肿瘤。人类胶质瘤根据间变程度或“去分化”表现进行分类。尽管这种组织学分类被广泛接受,但星形细胞瘤的广泛异质性使其病理分类相当困难。新的基因组规模的高通量基因表达谱技术,如DNA微阵列,正在成为新工具,通过发现每个阶段的新特异性标志物和途径,更准确地识别和表征不同的肿瘤程度。目前的工作报道了可能有助于区分肿瘤分级的有趣结果。这里呈现的数据提供了关于不同肿瘤阶段潜在分子基础的新证据。从这个意义上说,我们确定了对肿瘤进展至关重要的关键代谢途径在不同肿瘤阶段受到差异调节。另一方面,报告了关于Notch途径的显著发现,因为发现该受体家族的一些成员根据恶性程度差异表达。我们的结果清楚地指出了不同肿瘤阶段之间重要的分子差异,并表明需要更多研究来了解每个阶段特有的特定分子事件。这类研究是深入了解肿瘤生理学的第一步,这可能有助于更好、更精确地诊断胶质瘤。

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