Upregulation of DNA Metabolism-Related Genes Contributes to Radioresistance of Glioblastoma
Upregulation of DNA Metabolism-Related Genes Contributes to Radioresistance of Glioblastoma
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DNA 代谢相关基因的上调有助于胶质母细胞瘤的放射抗性
DOI：
10.1089/humc.2018.251
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发表时间：
2019
影响因子：
--
通讯作者：
Shao Chunlin
中科院分区：
文献类型：
--
作者：
Wang Chen;Zheng Wang;Yao Dan;Chen Qianping;Zhu Lin;Zhang Junlin;Pan Yan;Zhang Jianghong;Shao Chunlin
胶质母细胞瘤（GBM）是最常见的脑肿瘤，预后差。放射治疗是GBM患者的重要策略;然而，由于GBM的放射抗性，这种治疗仍然是姑息性的。胶质瘤干细胞（GSCs）作为胶质瘤细胞系中的一个亚群，在胶质瘤的放射抵抗和复发中起着关键作用。为了了解GSCs辐射抗性的关键基因，从Gene Expression Omnibus下载GSE 54660和GSE 60921的基因表达谱进行遗传和转录组学分析，以鉴定GSCs和GBM之间差异表达的潜在生物标志物基因。根据GSCs辐射反应基因谱筛选候选基因，筛选出DNAJC 9、GINS 2、STAT 1、CHAC 2、MT 1 M和ZNF 226等辐射抗性生物标志基因。将照射后GSC中差异表达的基因提交到基因本体论（GO）进行进一步富集分析和蛋白质-蛋白质相互作用（PPI）网络分析。最终筛选出一个与GINS 2有显著相关的模块，并鉴定出一系列参与DNA代谢的基因。总之，本研究提出了一组新的基因，差异表达的辐射抗性亚群内GBM和可能作为有前途的治疗靶点。
Glioblastomas (GBMs) are the most prevalent brain tumor and exhibit poor prognosis. Radiotherapy is an important strategy for GBMs patients; however, this care remains palliative because of GBMs' radioresistance. Glioma stem cells (GSCs), as a subpopulation residing at the apex of the hierarchy, have been believed to be a pivotal population in radioresistance and recurrence of GBMs. To know the key genes involved in radioresistance of GSCs, the gene expression profiles of GSE54660 and GSE60921 were downloaded from Gene Expression Omnibus for genetic and transcriptomic analysis to identify the potential biomarker genes differentially expressed between GSCs and GBMs. These candidate genes were then filtered by the GSCs gene profile responding to radiation and the radioresistant biomarker genes includingDNAJC9,GINS2,STAT1,CHAC2,MT1M, andZNF226were screened. The differentially expressed genes in GSCs post-irradiation were submitted to Gene Ontology (GO) for further enrichment analysis and protein-protein interaction (PPI) network analysis. A significant module correlated withGINS2was finally chosen and a series of genes participating in DNA metabolism were identified. In conclusion, this study propounds a set of novel genes that are differentially expressed in the radioresistant subpopulation within GBMs and could serve as promising therapeutic targets.