title: Bioinformatics analysis reveals disturbance mechanism of MAPK signaling pathway and cell cycle in Glioblastoma multiforme.
abstract: OBJECTIVE
  To analyze the reversal gene pairs and identify featured reversal genes related to mitogen-activated protein kinases (MAPK) signaling pathway and cell cycle in Glioblastoma multiforme (GBM) to reveal its pathogenetic mechanism.
  
  
  METHODS
  We downloaded the gene expression profile GSE4290 from the Gene Expression Omnibus database, including 81 gene chips of GBM and 23 gene chips of controls. The t test was used to analyze the DEGs (differentially expressed genes) between 23 normal and 81 GBM samples. Then some perturbing metabolic pathways, including MAPK (mitogen-activated protein kinases) and cell cycle signaling pathway, were extracted from KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database. Cancer genes were obtained from the database of Cancer Gene Census. The reversal gene pairs between DEGs and cancer genes were further analyzed in MAPK and cell cycle signaling pathway.
  
  
  RESULTS
  A total 8523 DEGs were obtained including 4090 up-regulated and 4433 down-regulated genes. Among them, ras-related protein rab-13(RAB13), neuroblastoma breakpoint family member 10 (NBPF10) and disks large homologue 4 (DLG4) were found to be involved in GBM for the first time. We obtained MAPK and cell cycle signaling pathways from KEGG database. By analyzing perturbing mechanism in these two pathways, we identified several reversal gene pairs, including NRAS (neuroblastoma RAS) and CDK2 (cyclin-dependent kinase 2), CCND1 (cyclin D1) and FGFR (fibroblast growth factor receptor). Further analysis showed that NRAS and CDK2 were positively related with GBM. However, FGFR2 and CCND1 were negatively related with GBM.
  
  
  CONCLUSIONS
  These findings suggest that newly identified DEGs and featured reversal gene pairs participated in MAPK and cell cycle signaling pathway may provide a new therapeutic line of approach to GBM.
authors: Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110023, China. Electronic address: wushengli321@hotmail.com.
authors: Wusheng
authors: W
authors: Li
authors: Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110023, China.
authors: Kai
authors: K
authors: Li
authors: Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110023, China.
authors: Li
authors: L
authors: Zhao
authors: Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110023, China.
authors: Huawei
authors: H
authors: Zou
mesh_terms: D016022:Case-Control Studies; D002453:Cell Cycle; D019295:Computational Biology; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: Bioinformatics analysis; Cell cycle; Cyclin-dependent kinase; Glioblastoma multiforme; MAPK signaling pathway