Analysis of Gene Expression Profiling in Meningioma: Deregulated Signaling Pathways Associated with Meningioma and EGFL6 Overexpression in Benign Meningioma Tissue and Serum

Abstract

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.

Gene expression profile comparison between colorectal cancer and adjacent normal tissues

“…Through KEGG pathway analysis, the upregulated genes were associated with 16 signal transduction pathways and the downregulated genes were associated with 7 signal transduction pathways; these included pathways that are known to be directly associated with the development of colorectal cancer or other cancers, such as ECM-receptor interaction. ECM-receptor interaction was identified to be significantly activated in patients with meningioma (25). Other key pathways that regulate cell adhesion, migration, proliferation and survival were downregulated, and have been associated with numerous tumors, including breast and thyroid carcinoma (26).…”

Decrease in serine protease HtrA1 expression correlates with grade and recurrence in meningiomas

“…At this point, a study of Wang et al with benign meningiomas takes attention. Wang et al demonstrated an up-regulation of TGFb signalling pathway in fibroblastic meningiomas [31].…”

Molecular characterization and expression analysis of mouse epidermal growth factor-like domain 8

“…First-strand cDNA was obtained via reverse transcription using 2 µg total RNA. The reaction was performed in 20 µl buffer containing 0.5 µg oligo(dT) [12][13][14][15][16][17][18] primer, 50 mM Tris-HCl (pH 8.3), 75 mM KCl, 3 mM MgCl 2 , 40 mM dithiothreitol, 0.5 mM deoxynucleotide triphosphate mixture, 10 units RNase inhibitor and 200 units Moloney murine leukemia virus reverse transcriptase (all from Invitrogen Life Technologies). After incubation at 37˚C for 60 min, the reaction was stopped via heating at 70˚C for 15 min.…”

“…EGFL6, an extracellular matrix protein, has been found in human subcutaneous adipose tissue and is a paracrine/autocrine growth factor of adipose tissue in obesity (15). EGFL6 is overexpressed in benign meningioma tissues and serum (16). Downregulation of EGFL8 expression has been observed in gastric cancer, and is significantly correlated with high tumor-node-metastasis stage and poor prognosis in gastric and colorectal cancer (17,18).…”