Preliminary Research On Differential Gene Expression Profile And The Relevant Signaling Pathways In Meningiomas

ObjectiveMeningioma is one of the most common tumors of the central nervous system. Up to date, the molecular mechanisms associated with meningioma tumorigenesis and progression are not elucidated. This research focuses on the differential gene expression profiles between meningiomas and brain arachnoidal tissue, and the signaling pathways involved, aiming at disclosing more of the molecular biological background of meningioma tumorigenesis.MethodsMicoarray analysis was performed for3fibroblastic meningiomas,3anaplastic meningiomas and3normal brain arachnoidal tissue. The differentially expressed (>2or<0.5-fold) genes between meningioma and brain arachnoidal tissue were extracted from the results, and put in the Kyoto Encyclopedia of Genes and Genomes pathways database to identify potential signaling pathways that may be involved in the tumorigenesis of meningioma. Further qRT-PCR (10fibroblastic meningiomas,6anaplastic meningiomas and3normal arachnoidal tissue) for mRNA of KEGG pathway associated genes were carried out to further validate the microarray results. Western blot was performed in6fibroblastic meningiomas and3normal arachoidal tissue, to detect expression of total and phosphorylated Akt. Total and phosphorylated FAK was also measured in3fibroblastic meningiomas,3anaplastic meningiomas and3normal arachnoidal tissue, by western blot analysis.ResultsCompared with normal brain arachnoidal tissue, there were5590up-regulated and3321down-regulated assessed genes in fibroblastic meningiomas. On the other hand, there were4583up-regulated and2791down-regulated assessed genes in fibroblastic meningiomas. Totally,13pathways with P value less than0.01were obtained, of which pathways in cancer (P=3.06*10-5) was the most significant pathway in fibroblastic meningioma. According to the differentially expressed genes, we figured out three sub-pathways in pathways in cancer that may be involved in the pathogenesis of fibroblastic meningioma, namely PI3K/Akt、cell cycle, and TGFβ signaling pathways.12significant (P<0.01) pathways in anaplastic meningiomas were generated. Of these pathways, focal adhesion (P=2.35*10-7) and ECM-receptor interaction (P=7.1*10-7) pathways, both mediated by integrin, were the most significantly different. qRT-PCR comfirmed the micro-array results by assay of the mRNA level of those differentially expressed genes involved in the KEGG pathways. As a most important protein within the PI3K/Akt pathway, total and phosphorylated Akt is higher in fibroblastic meningiomas than in normal arachnoidal tissue. As a most important protein involved both in the focal adhesion and ECM-receptor interaction pathways, total and phosphorylated FAK is higher in anaplastic meningiomas than in normal arachnoidal tissue.Conclusions Based on the differentially expressed genes obtained from micro-array results and the generally accepted interactions among those genes (KEGG pathways), we discovered in this research pathways that is significantly changed in fibroblastic and anaplastic meningiomas. After further analysis, we concluded, PI3K/Akt, cell cycle and TGFβ signaling pathways play role the tumorigenesis in fibroblastic meningiomas; activation of integrin mediated focal adhesion and ECM-receptor interaction pathways was significant in anaplastic meningiomas. Research on the genetic changes and relevant signal transduction pathways would offer important information for the elucidation of the molecular mechanisms of meningioma tumorigenesis and progression, and targeted molecular therapies for meningiomas.