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下调TTK表达改善胶质母细胞瘤裸鼠的生存预后
引用本文:冒平,王乙锠,王拓,杜昌旺,王茂德.下调TTK表达改善胶质母细胞瘤裸鼠的生存预后[J].中国临床神经外科杂志,2022,27(10):841-847.
作者姓名:冒平  王乙锠  王拓  杜昌旺  王茂德
作者单位:710061西安,西安交通大学第一附属医院神经外科(冒平、王乙锠、王拓、杜昌旺、王茂德)
摘    要:目的 探讨苏氨酸/酪氨酸激酶(TTK)在胶质母细胞瘤(GBM)中的表达变化及其作用。方法计算机检索TCGA数据库,利用生物信息学技术分析GBM组织TTK的表达水平及其与病人生存预后的关系。免疫组化染色分析我院生物样本库中60例脑胶质瘤组织的TTK表达水平。体外培养U251细胞,慢病毒转染构建TTK低表达细胞系,利用Alarma blue试剂盒测定细胞增殖能力,细胞克隆形成实验检测细胞克隆形成能力,流式细胞技术检测细胞凋亡和细胞周期。将不同TTK表达水平的U251细胞接种裸鼠构建移植瘤模型,分析TTK表达水平与移植瘤模型生存期的关系。结果生信分析结果显示,GBM组织TTK表达水平明显高于低级别胶质瘤及正常脑组织(P<0.05),TTK低表达GBM病人的总生存期更长(P<0.05)。我院60例胶质瘤中,高级别胶质瘤TTK高表达率(69.0%,29/42)明显高于低级别胶质瘤(16.7%,3/18;P<0.05)。下调TTK表达明显抑制U251细胞增殖、促进细胞凋亡(P<0.05)。TTK低表达裸鼠移植瘤模型的生存期明显延长(P<0.05)。结论 GBM组织TTK呈高水平表达,具有促进细胞增殖及抑制细胞凋亡的作用,与GBM的不良预后相关。

关 键 词:胶质母细胞瘤  苏氨酸/酪氨酸激酶(TTK)  裸鼠  细胞增殖  生存预后

Down-regulation of TTK improves the survival prognoses of nude mice bearing intracranial glioblastoma xenografts
MAO Ping,WANG Yi-chang,WANG Tuo,DU Chang-wang,WANG Mao-de.Down-regulation of TTK improves the survival prognoses of nude mice bearing intracranial glioblastoma xenografts[J].Chinese Journal of Clinical Neurosurgery,2022,27(10):841-847.
Authors:MAO Ping  WANG Yi-chang  WANG Tuo  DU Chang-wang  WANG Mao-de
Affiliation:Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
Abstract:Objective To investigate the expression and role of threonine/tyrosine kinase (TTK) in glioblastoma (GBM). Methods The TCGA database was searched by computer, and the expression level of TTK in GBM tissuesand its relationship with the prognosis of patients were analyzed by bioinformatics methods. Immunohistochemical staining was used to analyze the expression of TTK in 60 glioma tissues obtained from our hospital biobank. U251 cells were cultured in vitro and transfected with lentivirus to construct TTK low expression cell line. Alarma blue kit was used to detect cell proliferation, cell clone formation assay was used to detect cell clone formation, and flow cytometry was used to detect cell apoptosis and cell cycle. U251 cells with different TTK expression levels were transplanted into nude mice to establish xenograft tumor models, and the relationship between TTK expression levels and the survival of xenograft tumor models was analyzed. Results The results of bioinformatics analysis showed that the expression level of TTK in GBM tissues was significantly higher than that in low-grade glioma and normal brain tissues (P<0.05), and the overall survival time of GBM patients with low TTK expression was significantly longer (P<0.05). Of 60 glioma obtained from our hospital biobank, the high expression rate of TTK in high-grade gliomas (69.0%, 29/42) was significantly higher than that in low-grade gliomas (16.7%, 3/18; P<0.05). Down-regulation of TTK expression significantly inhibited the proliferation and promoted apoptosis of U251 cells (P<0.05). The survival time of TTK low expression xenograft model of nude mice was significantly prolonged (P<0.05). Conclusions The high level of TTK expression in GBM tissue can promote cell proliferation and inhibit cell apoptosis, which is related to the poor prognosis of GBM.
Keywords:Glioblastoma  Threonine/tyrosine kinase (TTK)  Cell proliferation  Survival prognosis  Nude mice
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