Analysis of gene expression profiling in meningioma: deregulated signaling pathways associated with meningioma and EGFL6 overexpression in benign meningioma tissue and serum.
Analysis of gene expression profiling in meningioma: deregulated signaling pathways associated with meningioma and EGFL6 overexpression in benign meningioma tissue and serum.
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脑膜瘤基因表达谱分析：与良性脑膜瘤组织和血清中脑膜瘤和 EGFL6 过表达相关的信号通路失调
DOI：
10.1371/journal.pone.0052707
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mao Y
中科院分区：
文献类型：
--
作者：
Wang X;Gong Y;Wang D;Xie Q;Zheng M;Zhou Y;Li Q;Yang Z;Tang H;Li Y;Hu R;Chen X;Mao Y
脑膜瘤发病机制的分子机制尚未完全阐明。在这项研究中，我们利用Affymetrix基因芯片Human U133 Plus 2.0阵列建立脑膜瘤和脑蛛网膜组织的差异基因表达谱。KEGG通路分析表明，PI3K/Akt和TGFβ信号通路在成纤维性脑膜瘤中上调，在间变性脑膜瘤中灶性粘附和ecm受体相互作用通路被激活。微阵列分析显示，EGFL6是纤维母细胞脑膜瘤中上调最多的基因之一。实时荧光定量PCR结果显示，良性脑膜瘤的EGFL6 mRNA表达水平明显高于脑蛛网膜组织、非典型脑膜瘤和间变性脑膜瘤（P<0.001）。EGFL6基因在卵巢癌中也有高表达，但在其他肿瘤中表达较低。ELISA分析显示，良性脑膜瘤和卵巢癌患者血清EGFL6水平最高（良性脑膜瘤平均浓度为672 pg/ml，卵巢癌平均浓度为616 pg/ml）。然而，健康人群和患有其他肿瘤的患者血清EGFL6水平较低。综上所述，我们认为PI3K/Akt和整合素介导的信号通路的激活分别参与了良性和间变性脑膜瘤的发病过程。我们也提出证据表明EGFL6在良性脑膜瘤组织和血清中过表达。
Molecular mechanisms underlying the pathogenesis of meningioma are not fully elucidated. In this study, we established differential gene expression profiles between meningiomas and brain arachnoidal tissue by using Affymetrix GeneChip Human U133 Plus 2.0 Array. KEGG pathway analysis demonstrated that PI3K/Akt and TGFβ signaling pathways were up-regulated in fibroblastic meningioma, and focal adhesion and ECM-receptor interaction pathways were activated in anaplastic meningioma. EGFL6 was one of the most up-regulated genes in fibroblastic meningioma by microarray analysis. Quantitative real-time PCR demonstrated that benign meningiomas had significantly higher levels of EGFL6 mRNA than brain arachnoidal tissue and atypical and anaplastic meningiomas (P<0.001). EGFL6 gene was also highly expressed in ovarian cancer, but expressed lowly in other investigated tumors. ELISA analysis showed that patients with benign meningiomas and ovarian cancers had the highest serum levels of EGFL6 (mean concentration: 672 pg/ml for benign meningiomas, and 616 pg/ml for ovarian cancers). Healthy people and patients with other tumors, however, had low levels of serum EGFL6. In conclusion, we proposed that activation of PI3K/Akt and integrin-mediated signaling pathways was involved in the pathogenesis of benign and anaplastic meningiomas, respectively. We also presented evidence that EGFL6 was overexpressed in benign meningioma tissues and serum.
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影响因子：
4.3
作者：
Oberauer, Rupert;Rist, Wolfgang;Neubauer, Heike
通讯作者：
Neubauer, Heike
影响因子：
64.5
作者：
Fujiwara H;Ferreira M;Donati G;Marciano DK;Linton JM;Sato Y;Hartner A;Sekiguchi K;Reichardt LF;Watt FM
通讯作者：
Watt FM
影响因子：
10.5
作者：
McLean, GW;Komiyama, NH;Frame, MC
通讯作者：
Frame, MC
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP
影响因子：
4.8
作者：
Fathallah-Shaykh, HM;He, B;Farooq, K
通讯作者：
Farooq, K