Table_4_CENPA acts as a prognostic factor that relates to immune infiltrates in gliomas.XLSX

BackgroundGlioma 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.
MethodsThe 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.
ResultsCENPA 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.
ConclusionCENPA may act as a prognostic factor in patients with glioma and provide a novel target for the treatment of gliomas.

背景
神经胶质瘤（Glioma）是中枢神经系统（central nervous system, CNS）最常见的原发性肿瘤。着丝粒蛋白A（Centromere protein A, CENPA）在保障有丝分裂正常进行中发挥关键作用。目前关于CENPA对神经胶质瘤的影响的相关报道较为少见。本研究旨在探讨异常表达的CENPA是否会促进神经胶质瘤进展，以及其潜在的作用机制。

方法
本研究通过GEPIA网站、癌症基因组图谱（The Cancer Genome Atlas, TCGA）以及基因表达综合数据库（Gene Expression Omnibus, GEO）分析CENPA在神经胶质瘤中的表达情况，并通过实时定量聚合酶链反应（real-time quantitative polymerase chain reaction, qRT-PCR）及临床样本的免疫组化染色对结果进行验证。基于从中国神经胶质瘤基因组图谱（Chinese Glioma Genome Atlas, CGGA）及UCSC Xena下载的RNA测序数据与临床资料，采用Kaplan-Meier（KM）生存分析探究CENPA基因表达与神经胶质瘤患者预后价值之间的关联，并评估CENPA表达与临床病理特征的相关性。本研究还使用了两种神经胶质瘤细胞系开展细胞计数试剂盒-8（Cell Counting Kit-8, CCK8）实验、划痕愈合实验，同时通过基因集富集分析（gene set enrichment analysis, GSEA）、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析、基因本体（Gene Ontology, GO）富集分析、免疫浸润分析、替莫唑胺（temozolomide, TMZ）敏感性分析及单细胞测序分析，以探究CENPA高表达的潜在机制及其对神经胶质瘤发生发展的影响。最后，本研究基于CENPA的表达水平开展Cox回归分析，以预测神经胶质瘤患者的预后情况。

结果
CENPA在神经胶质瘤组织样本中显著上调，且与患者预后密切相关。下调CENPA的表达可抑制神经胶质瘤细胞的迁移与增殖能力。此外，CENPA的表达水平与肿瘤分级、原发-复发-继发（primary-recurrent-secondary, PRS）分型、异柠檬酸脱氢酶（isocitrate dehydrogenase, IDH）突变状态及1p19q共缺失状态均存在显著相关性。进一步研究发现，CENPA可作为神经胶质瘤的独立预后因子，其主要通过干扰有丝分裂的正常进程，并调控有利于神经胶质瘤发展的肿瘤免疫微环境发挥作用。

结论
CENPA可作为神经胶质瘤患者的预后评估因子，同时为神经胶质瘤的治疗提供全新的靶点。