Zhong Sheng, Wu Bo, Dong Xuechao, Han Yujuan, Jiang Shanshan, Zhang Ying, Bai Yang, Luo Sean X, Chen Yong, Zhang Huimao, Zhao Gang
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China; Clinical College, Jilin University, Changchun, China.
Clinical College, Jilin University, Changchun, China.
World Neurosurg. 2018 Jan;109:e329-e342. doi: 10.1016/j.wneu.2017.09.176. Epub 2017 Oct 6.
The aim of this study is to identify novel targets of diagnosis, therapy, and prognosis for glioblastoma, as well as to verify the therapeutic effect of JNJ-7706621 regarding glioblastoma.
The gene expression profiles of GSE42656, GSE50161, and GSE86574 were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified with comparison between gene expression profiles of the glioblastoma tissues and normal tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analyses were performed. Quantitative reverse transcription polymerase chain reaction and survival curve analysis were also conducted to verify the correlation between expression of hub genes and prognosis. Moreover, in vitro, MTT assay, colony-forming assay, the scratch assay, and flow cytometry were performed to verify the therapeutic effect of JNJ-7706621.
AURKA, NDC80, KIF4A, and NUSAP1 were identified as hub genes after PPI network analysis. Differential expression of those genes was detected between human normal glial cells and glioblastoma cells by quantitative reverse transcription polymerase chain reaction (P < 0.05), and the survival curve analysis showed that the patients with low expression of gene AURKA, NDC80, KIF4A, and NUSAP1 had a significant favorable prognosis (P < 0.05). In vitro assays showed that JNJ-7706621 inhibited glioblastoma cellular viability, proliferation, and migration via inducing glioblastoma cells apoptosis.
AURKA, NDC80, KIF4A, and NUSAP1 were significantly more highly expressed in glioblastoma cells than in human normal glial cell. Patients with low expression of those 4 genes had a favorable prognosis. JNJ-7706621 was a potential drug in treatment of patients with glioblastoma.
本研究旨在确定胶质母细胞瘤诊断、治疗和预后的新靶点，并验证JNJ-7706621对胶质母细胞瘤的治疗效果。
分别从基因表达综合数据库获取GSE42656、GSE50161和GSE86574的基因表达谱。通过比较胶质母细胞瘤组织和正常组织的基因表达谱来鉴定差异表达基因（DEGs）。进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）分析以及蛋白质-蛋白质相互作用（PPI）网络分析。还进行了定量逆转录聚合酶链反应和生存曲线分析，以验证枢纽基因表达与预后之间的相关性。此外，在体外进行MTT试验、集落形成试验、划痕试验和流式细胞术，以验证JNJ-7706621的治疗效果。
通过PPI网络分析确定AURKA、NDC80、KIF4A和NUSAP1为枢纽基因。通过定量逆转录聚合酶链反应检测到这些基因在人正常神经胶质细胞和胶质母细胞瘤细胞之间存在差异表达（P < 0.05），生存曲线分析表明，AURKA、NDC80、KIF4A和NUSAP1基因低表达的患者预后明显较好（P < 0.05）。体外试验表明，JNJ-7706621通过诱导胶质母细胞瘤细胞凋亡来抑制胶质母细胞瘤细胞的活力、增殖和迁移。
AURKA、NDC80、KIF4A和NUSAP1在胶质母细胞瘤细胞中的表达明显高于人正常神经胶质细胞。这4个基因低表达的患者预后良好。JNJ-7706621是治疗胶质母细胞瘤患者的一种潜在药物。
