Wang Bo, Wei Wei, Long Shengrong, Wang Lesheng, Yang Bin, Wu Du, Li Zhengwei, Li Zhiqiang, Arshad Muhammad, Li Xiang, Chen Jincao
Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Brain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan, China.
Front Neurol. 2022 Oct 19;13:1015221. doi: 10.3389/fneur.2022.1015221. eCollection 2022.
Glioma is the most common primary tumor of the central nervous system (CNS). Centromere protein A (CENPA) plays an essential role in ensuring that mitosis proceeds normally. The effect of CENPA on glioma is rarely reported. However, the current study aims to explore whether aberrant CENPA expression promotes glioma progression and the potential mechanisms involved.
The GEPIA website, The Cancer Genome Atlas, and the Gene Expression Omnibus (GEO) were used to assess the expression of CENPA in glioma. The results were validated by real-time quantitative polymerase chain reaction and immunohistochemical staining of clinical samples. The relationship between the expression and prognostic value of the CENPA gene in glioma was investigated by Kaplan-Meier (KM) survival analysis with RNA-seq and clinical profiles downloaded from the Chinese Glioma Genome Atlas (CGGA) and UCSC Xena. The association between CENPA and clinical characteristics was also evaluated. Cell Counting Kit-8 (CCK8) assay, wound healing assay using two glioma cell lines, gene set enrichment analysis (GSEA), KEGG and gene ontology (GO) enrichment analysis, immune infiltration analysis, temozolomide (TMZ) sensitivity analysis, and single-cell sequence analysis were performed to explore the underlying mechanisms of high CENPA expression and its effect on glioma development. Finally, we performed a Cox analysis based on the expression of CENPA to predict patient prognosis.
CENPA was significantly upregulated in glioma tissue samples and correlated with patient prognosis. Moreover, the downregulation of CENPA inhibited the migration and proliferation of glioma cells. In addition, the expression level of CENPA was significantly correlated with the grade, primary-recurrent-secondary (PRS) type, IDH mutation status, and 1p19q codeletion status. Furthermore, CENPA could serve as an independent prognostic factor for glioma that mainly interferes with the normal progression of mitosis and regulates the tumor immune microenvironment favoring glioma development.
CENPA may act as a prognostic factor in patients with glioma and provide a novel target for the treatment of gliomas.
胶质瘤是中枢神经系统（CNS）最常见的原发性肿瘤。着丝粒蛋白A（CENPA）在确保有丝分裂正常进行中起重要作用。CENPA对胶质瘤的影响鲜有报道。然而，当前研究旨在探讨CENPA表达异常是否促进胶质瘤进展及其潜在机制。
利用GEPIA网站、癌症基因组图谱（The Cancer Genome Atlas）和基因表达综合数据库（Gene Expression Omnibus，GEO）评估胶质瘤中CENPA的表达。通过实时定量聚合酶链反应和临床样本的免疫组织化学染色验证结果。利用从中国胶质瘤基因组图谱（Chinese Glioma Genome Atlas，CGGA）和加州大学圣克鲁兹分校Xena数据库下载的RNA测序和临床资料，通过Kaplan-Meier（KM）生存分析研究胶质瘤中CENPA基因表达与预后价值之间的关系。还评估了CENPA与临床特征之间的关联。采用细胞计数试剂盒-8（CCK8）检测、使用两种胶质瘤细胞系的伤口愈合试验、基因集富集分析（GSEA）、KEGG和基因本体（GO）富集分析、免疫浸润分析、替莫唑胺（TMZ）敏感性分析和单细胞序列分析，以探讨CENPA高表达的潜在机制及其对胶质瘤发展的影响。最后，基于CENPA的表达进行Cox分析以预测患者预后。
CENPA在胶质瘤组织样本中显著上调，并与患者预后相关。此外，CENPA的下调抑制了胶质瘤细胞的迁移和增殖。此外，CENPA的表达水平与分级、原发-复发-继发（PRS）类型、异柠檬酸脱氢酶（IDH）突变状态和1p19q共缺失状态显著相关。此外，CENPA可作为胶质瘤的独立预后因素，主要干扰有丝分裂的正常进程并调节有利于胶质瘤发展的肿瘤免疫微环境。
CENPA可能是胶质瘤患者的预后因素，并为胶质瘤治疗提供新的靶点。
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