Gene expression profiling in human high-grade astrocytomas.

Gene expression profiling in human high-grade astrocytomas.
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人类高级星形细胞瘤的基因表达谱。

DOI:
10.1155/2011/245137
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发表时间:
2011
影响因子:
--
通讯作者:
Gao C
Gao C
中科院分区:
其他
文献类型:
--
作者:
Liu Z;Yao Z;Li C;Lu Y;Gao C

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弥漫性星形细胞瘤(WHO II级)有自发进展为间变性星形细胞瘤(WHO III级)和/或胶质母细胞瘤(WHO IV级)的趋势。然而,星形细胞瘤进展的分子基础仍然知之甚少。在目前的研究中,实现这一目标的一个重要的第一步是建立肿瘤的基因表达谱的基础上的分类。我们使用基因表达谱分析,(分层聚类(HCL)和主成分分析(PCA))和监督(微阵列预测分析(PAM))学习方法,以证明星形细胞瘤(ACM)的三种不同基因表达特征的存在,其对应于弥漫性或低级别星形细胞瘤。(WHO II级)、间变性星形细胞瘤(WHO III级)和多形性胶质母细胞瘤(WHO IV级)。我们还展示了一个171基因为基础的分类器,这些星形细胞瘤的病理/分子亚型之间的区别的特点。这些结果进一步定义了星形细胞瘤的分子亚型,并可能用于定义潜在的靶点,进一步完善分层治疗方法。此外,这项研究表明,结合基因表达分析与详细的注释途径和基因本体(GO)类别资源,适用于高度富集的正常和肿瘤人群,它可以产生的星形细胞瘤的关键生物学机制的理解。
Diffuse astrocytoma of (WHO grade II) has a tendency to progress spontaneously to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). However, the molecular basis of astrocytoma progression is still poorly understood. In current study, an essential initial step toward this goal is the establishment of the taxonomy of tumors on the basis of their gene expression profiles. We have used gene expression profiling, unsupervised (hierarchal cluster (HCL) and principal component analysis (PCA)) and supervised (prediction analysis for microarrays (PAM)) learning methods, to demonstrate the presence of three distinct gene expression signatures of astrocytomas (ACMs), which correspond to diffuse or low-grade astrocytoma (WHO grade II), Anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV). We also demonstrate a 171 gene-based classifier that characterize the distinction between these pathologic/molecular subsets of astrocytomas. These results further define molecular subtypes of astrocytomas and may potentially be used to define potential targets and further refine stratification approaches for therapy. In addition, this study demonstrates that combining gene expression analysis with detailed annotated pathway and gene ontology (GO) category resources was applied to highly enriched normal and tumor population; it can yield an understanding of the critical biological mechanism of astrocytomas.
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