1.潍坊医学院;2.临沂市人民医院神经外科;3.北京市神经外科研究所/首都医科大学附属北京天坛医院，北京 100070
孙强（1991—)，男，住院医师，硕士，主要从事脑肿瘤临床与基础研究。
张健（1966—），男，临沂市人民医院神经外科科室主任，主任医师，博士，主要从事脑肿瘤、脑功能的临床与基础研究，Email: honest20699@126.com。
山东省医药卫生科技发展计划项目（202104040538）；临沂市科技发展计划项目（202120064）。
1.Weifang Medical University， Weifang， Shandong 261053， China;2.Department of Neurosurgery， Linyi People’s Hospital， Linyi， Shandong 276000， China;3.Beijing Neurosurgical Institute/Beijing Tiantan Hospital， Capital Medical University， Beijing 100070， China
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目的 探究着丝粒蛋白F（CENPF）在脑胶质瘤中的表达及预后分析。方法 通过对癌症基因组图谱（TCGA）和中国脑胶质瘤图谱（CGGA）数据库进行生物信息分析，比较CENPF在低级别胶质瘤（LGG）、胶质母细胞瘤（GBM）和癌旁组织中的表达差异以及与患者预后之间的关系，并在数据库中对CENPF mRNA与P53、Ki-67以及IDH-1分型进行相关性分析。采用实时荧光定量PCR（qRT-PCR）法检测CENPF mRNA表达水平，免疫组织化学法和Western blotting法检测癌旁组织和不同级别胶质瘤组织中CENPF表达水平。多因素COX分析CENPF与临床病理参数及患者预后的关系，并绘制Kaplan‐Meier生存曲线。利用TCGA数据库对CENPF进行KEGG富集分析，探索该基因在胶质瘤中发展中可能参与的信号通路。结果 CENPF表达水平与胶质瘤WHO分级呈正相关，且CENPF高表达的胶质瘤患者生存时间短于低表达患者。数据库相关性分析显示CENPF mRNA与P53、Ki-67以及IDH-1野生型呈正相关。qRT-PCR实验结果表明CENPF mRNA在胶质瘤组织中表达增高，免疫组织化学和Western blotting实验结果表明CENPF表达与WHO等级呈正相关。临床病理参数分析表明在胶质瘤组织中CENPF表达情况与胶质瘤WHO分级（P=0.002）、P53（P=0.016）、Ki-67（P<0.001）表达有关。多因素COX分析显示WHO分级（P<0.001）、CENPF表达（P=0.008）、P53（P=0.003）和Ki-67（P=0.006）表达为胶质瘤患者预后不良的危险因素。Kaplan‐Meier生存曲线表明CENPF高表达的胶质瘤患者生存时间短于低表达患者（P<0.0001）。KEGG富集分析显示CENPF在参与细胞周期、DNA复制、WNT/beta-catenin、mTORC1等通路中具有显著富集。结论 CENPF在胶质瘤组织中表达增高，其表达与WHO分级、Ki-67以及P53分型相关；CENPF可作为判断胶质瘤患者预后的生物标志物。
Objective To investigate the expression of centromere protein F （CENPF） in glioma and its prognostic significance.Methods A bioinformatics analysis was performed based on TCGA and CGGA databases to compare the expression of CENPF in low-grade glioma， glioblastoma， and adjacent tissue and analyze its association with prognosis， and a correlation analysis was performed to investigate the correlation of the mRNA expression of CENPF with P53， Ki-67， and IDH-1 typing. Quantitative real-time PCR was used to measure the mRNA expression of CENPF， and immunohistochemistry and Western blotting were used to measure the expression of CENPF in adjacent tissue and tissue samples of glioma with different grades. A multivariate Cox regression analysis was used to investigate the association between clinicopathological parameters and prognosis， and Kaplan-Meier survival curves were plotted. TCGA database was used to perform the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis of CENPF to explore the possible signaling pathways involved in the development of glioma.Results The bioinformatics analysis showed that the expression of CENPF was positively correlated with WHO classification of glioma， and the glioma patients with high CENPF expression had a shorter survival time than those with low expression （P <0.05）. The correlation analysis showed that the mRNA expression of CENPF was significantly positively correlated with P53， Ki-67， and IDH-1 wild type. Quantitative real‐time PCR showed that there was an increase in the mRNA expression of CENPF， and immunohistochemistry and Western blotting showed a positive correlation between CENPF expression and WHO grade （P <0.001）. The analysis of clinicopathological parameters showed that the expression of CENPF in glioma tissue was associated with WHO grade （P = 0.002）， P53 （P = 0.016）， and Ki-67 （P <0.001）. The multivariate Cox regression analysis showed that WHO grade （P <0.001）， CENPF expression （P = 0.008）， P53 expression （P = 0.003）， and Ki-67 expression （P = 0.006） were risk factors for poor prognosis of glioma patients. The Kaplan‐Meier survival curves showed that the glioma patients with high CENPF expression had a significantly shorter survival time than those with low expression （P <0.0001）. The KEGG pathway enrichment analysis showed that CENPF was significantly enriched in the pathways involved in cell cycle， DNA replication， WNT/beta-catenin， and mTORC1.Conclusion There is an increase expression of CENPF in glioma tissue， and its expression is correlated with WHO classification， P53， and Ki-67 typing. Therefore， CENPF can be used as a biomarker to judge the prognosis of glioma patients.
引用本文
孙强,孟祥龙,薛正淳,杜飞,张健,张墨轩456.着丝粒蛋白F在胶质瘤组织中的表达及预后分析[J].国际神经病学神经外科学杂志,2023,50(1):1-8111SUN Qiang, MENG Xianglong, XUE Zhengchun, DU Fei, ZHANG Jian, ZHANG Moxuan222. Expression and prognostic analysis of centromere protein F in glioma tissue[J]. Journal of International Neurology and Neurosurgery,2023,50(1):1-8
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- 收稿日期:2022-08-15
- 最后修改日期:2023-02-09
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- 在线发布日期: 2023-04-12
