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全基因组表达谱分析确定了脑膜瘤中特定的失调通路。

Genome wide expression profiling identifies specific deregulated pathways in meningioma.

作者信息

Keller Andreas, Ludwig Nicole, Backes Christina, Romeike Bernd F M, Comtesse Nicole, Henn Wolfram, Steudel Wolf-Ingo, Mawrin Christian, Lenhof Hans-Peter, Meese Eckart

机构信息

Center for Bioinformatics, Saarland University, Building E.1.1, Saarbrücken 66041, Germany.

出版信息

Int J Cancer. 2009 Jan 15;124(2):346-51. doi: 10.1002/ijc.23942.

Abstract

Genome-wide expression signatures improve the understanding of tumor biology. We performed expression profiling of 24 meningioma including 8 of each WHO grade and 2 dura controls analyzing 55.000 transcripts including 18.300 known genes. We compared expression in meningioma vs. dura, expression of low grade (WHO I) vs. higher-grade (WHO II and WHO III) tumors and expression of meningothelial and syncytial meningioma vs. fibroblastic meningioma. Overall expression was significantly decreased in meningioma compared to dura and in meningothelial and syncytial compared to fibroblastic meningioma. Gene expression was exemplarily confirmed by immunohistochemistry using independent samples. Applying our statistical gene set analysis toolkit "GeneTrail", we identified significantly deregulated biochemical pathways using Kyoto encyclopedia of genes and genomes and Transpath databases. Kyoto encyclopedia of genes and genomes pathways with decreased expression in meningioma included cell adhesion molecules (p<0.0001) and cytokine-cytokine receptor interactions (p<0.0001). Pathways with increased expression included several metabolic pathways. Extended expression profiling by a novel statistical gene set enrichment identified pathways that have previously not been associated with meningioma.

摘要

全基因组表达特征有助于加深对肿瘤生物学的理解。我们对24例脑膜瘤进行了表达谱分析,其中包括世界卫生组织(WHO)各分级的8例以及2例硬脑膜对照,分析了55000个转录本,包括18300个已知基因。我们比较了脑膜瘤与硬脑膜的表达、低级别(WHO I级)与高级别(WHO II级和WHO III级)肿瘤的表达以及脑膜内皮型和合体细胞型脑膜瘤与纤维型脑膜瘤的表达。与硬脑膜相比,脑膜瘤的整体表达显著降低;与纤维型脑膜瘤相比,脑膜内皮型和合体细胞型脑膜瘤的表达也显著降低。通过使用独立样本的免疫组织化学对基因表达进行了验证。应用我们的统计基因集分析工具包“GeneTrail”,我们利用京都基因与基因组百科全书(KEGG)和Transpath数据库鉴定出显著失调的生化途径。在脑膜瘤中表达降低的KEGG途径包括细胞黏附分子(p<0.0001)和细胞因子-细胞因子受体相互作用(p<0.0001)。表达增加的途径包括几种代谢途径。通过一种新的统计基因集富集进行的扩展表达谱分析鉴定出了以前未与脑膜瘤相关联的途径。

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