Wang Rui, Wei Jun, Li Zhaohui, Tian Yu, Du Chao
Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Science and Education, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Oncol Lett. 2018 Mar;15(3):2807-2814. doi: 10.3892/ol.2017.7660. Epub 2017 Dec 20.
The aim of the present study was to identify the common molecular mechanisms of multiple glioma subtypes, including astrocytoma, glioblastoma and oligodendroglioma, in addition to the specific mechanisms of different types. The gene expression profile set GSE4290 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) from three types of glioma, relative to non-tumor tissue, were calculated by the t-test method with a linear regression model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs was performed. GeneVenn online analysis software was used for the comparison of the DEGs between subtypes. A total of 795 DEGs, including 619 up and 176 downregulated DEGs were screened from the astrocytoma expression profiles; these were enriched in the KEGG pathways of 'neuroactive ligand-receptor interaction' (upregulated) and 'Wnt signaling pathway' (downregulated). Protein-protein interaction networks for astrocytoma, glioblastoma and oligodendroglioma were constructed with 1,617, 7,027 and 1,172 pairs, respectively. A total of 595 common DEGs were obtained between the three subtypes, which were enriched in pathways associated with neural signaling. Glioblastoma is a subtype of astrocytoma; there were 195 DEGs common between these subtypes that were not also associated with oligodendroglioma. DEGs unique to astrocytoma, glioblastoma and oligodendroglioma were associated with the development of the nervous system, the cell cycle and cell matrix components, respectively. The screened DEG p53 gene is likely to be critical for glioma development, including via the Wnt and p53 signaling pathways. Brain-derived neurotrophic factor and cyclin-dependent kinase 1 genes were also likely to be important in the mechanism of glioma development, and were associated with the cell cycle and p53 signaling pathways. Immune system-associated and cell matrix component pathways may be unique signaling pathways associated with astrocytoma and oligodendroglioma, respectively.
本研究的目的是确定多种胶质瘤亚型（包括星形细胞瘤、胶质母细胞瘤和少突胶质细胞瘤）的共同分子机制，以及不同类型的特定机制。基因表达谱集GSE4290从基因表达综合数据库下载。采用线性回归模型的t检验方法计算三种类型胶质瘤相对于非肿瘤组织的差异表达基因（DEG）。对DEG进行京都基因与基因组百科全书（KEGG）通路富集分析。使用GeneVenn在线分析软件比较各亚型之间的DEG。从星形细胞瘤表达谱中筛选出795个DEG，包括619个上调和176个下调的DEG；这些基因在KEGG通路“神经活性配体-受体相互作用”（上调）和“Wnt信号通路”（下调）中富集。分别构建了星形细胞瘤、胶质母细胞瘤和少突胶质细胞瘤的蛋白质-蛋白质相互作用网络，分别有1617、7027和1172对。在三种亚型之间共获得595个共同的DEG，这些基因在与神经信号相关的通路中富集。胶质母细胞瘤是星形细胞瘤的一种亚型；这些亚型之间有195个共同的DEG，这些DEG与少突胶质细胞瘤无关。星形细胞瘤、胶质母细胞瘤和少突胶质细胞瘤特有的DEG分别与神经系统发育、细胞周期和细胞基质成分有关。筛选出的DEG p53基因可能对胶质瘤的发展至关重要，包括通过Wnt和p53信号通路。脑源性神经营养因子和细胞周期蛋白依赖性激酶1基因在胶质瘤发展机制中也可能很重要，并与细胞周期和p53信号通路有关。免疫系统相关通路和细胞基质成分通路可能分别是与星形细胞瘤和少突胶质细胞瘤相关的独特信号通路。
