Stangeland Biljana, Mughal Awais A, Grieg Zanina, Sandberg Cecilie Jonsgar, Joel Mrinal, Nygård Ståle, Meling Torstein, Murrell Wayne, Vik Mo Einar O, Langmoen Iver A
Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
SFI-CAST Biomedical Innovation Center, Oslo University Hospital, Oslo, Norway.
Oncotarget. 2015 Sep 22;6(28):26192-215. doi: 10.18632/oncotarget.4613.
Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures. The expression of these genes was confirmed in clinical samples (TCGA and REMBRANDT). The first nine genes were highly co-expressed in all GBM subtypes and were part of the same protein-protein interaction network. Furthermore, their combined up-regulation correlated negatively with patient survival in the mesenchymal GBM subtype. Using targeted proteomics and the COGNOSCENTE database we linked these genes to GBM signalling pathways.Nine genes: PBK, CENPA, KIF15, DEPDC1, CDC6, DLG7, KIF18A, EZH2 and HMMR should be further explored as targets for treatment of GBM.
胶质母细胞瘤（GBM）是最常见且最致命的原发性脑肿瘤。据认为，胶质母细胞瘤干细胞（GSCs）在抗治疗性方面至关重要。因此，有充分的理由靶向这些细胞以开发新的分子疗法。为了鉴定GSCs中的分子靶点，我们使用微阵列比较了GSCs与成人脑内神经干细胞（NSCs）的基因表达。生物信息学筛选确定了20个基因（PBK/TOPK、CENPA、KIF15、DEPDC1、CDC6、DLG7/DLGAP5/HURP、KIF18A、EZH2、HMMR/RHAMM/CD168、NOL4、MPP6、MDM1、RAPGEF4、RHBDD1、FNDC3B、FILIP1L、MCC、ATXN7L4/ATXN7L1、P2RY5/LPAR6和FAM118A），这些基因在GSC培养物中持续表达，而在NSC培养物中持续不表达。这些基因的表达在临床样本（TCGA和REMBRANDT）中得到了证实。前九个基因在所有GBM亚型中高度共表达，并且是同一蛋白质-蛋白质相互作用网络的一部分。此外，它们的联合上调与间充质GBM亚型患者的生存率呈负相关。使用靶向蛋白质组学和COGNOSCENTE数据库，我们将这些基因与GBM信号通路联系起来。九个基因：PBK、CENPA、KIF15、DEPDC1、CDC6、DLG7、KIF18A、EZH2和HMMR应作为GBM治疗靶点进一步探索。
