PDF(Pubmed)
Abstract：
Glioblastoma (GBM) is characterized by significant heterogeneity, leading to poor survival outcomes for patients, despite the implementation of comprehensive treatment strategies. The roles of cyclin A2 (CCNA2) and NIMA related kinase 2 (NEK2) have been extensively studied in numerous cancers, but their specific functions in GBM remain to be elucidated. The present study aimed to investigate the potential molecular mechanisms of CCNA2 and NEK2 in GBM. CCNA2 and NEK2 expression and prognosis in glioma were evaluated by bioinformatics methods. In addition, the distribution of CCNA2 and NEK2 expression in GBM subsets was determined using pseudo-time analysis and tricycle position of single-cell sequencing. Gene Expression Omnibus and Kyoto Encyclopedia of Genes and Genome databases were employed and enrichment analyses were conducted to investigate potential signaling pathways in GBM subsets and a nomogram was established to predict 1-, 2- and 3-year overall survival probability in GBM. CCNA2 and NEK2 expression levels were further validated by western blot analysis and immunohistochemical staining in GBM samples. High expression of CCNA2 and NEK2 in glioma indicates poor clinical outcomes. Single-cell sequencing of GBM revealed that these genes were upregulated in a subset of positive neural progenitor cells (P-NPCs), which showed significant proliferation and progression properties and may activate G2M checkpoint pathways. A comprehensive nomogram predicts 1-, 2- and 3-year overall survival probability in GBM by considering P-NPCs, age, chemotherapy and radiotherapy scores. CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle, thus indicating the potential of novel therapy directed to CCNA2 and NEK2 in GBM.
摘要：
胶质母细胞瘤(GBM)具有显著的异质性,导致患者生存结果不佳，尽管实施了综合治疗策略。细胞周期蛋白A2(CCNA2)和NIMA相关激酶2(NEK2)在许多癌症中的作用已被广泛研究。但它们在GBM中的具体功能仍有待阐明。本研究旨在探讨CCNA2和NEK2在GBM中的潜在分子机制。通过生物信息学方法评估CCNA2和NEK2在胶质瘤中的表达和预后。此外,CCNA2和NEK2表达在GBM亚群中的分布使用假时间分析和单细胞测序的三轮位置确定。基因表达Omnibus和京都百科全书的基因和基因组数据库的使用和富集分析进行研究，以研究潜在的信号通路在GBM亚群和列线图建立预测1-，GBM的2年和3年总生存概率。通过蛋白质印迹分析和免疫组织化学染色在GBM样品中进一步验证CCNA2和NEK2表达水平。神经胶质瘤中CCNA2和NEK2的高表达表明临床预后差。GBM的单细胞测序显示，这些基因在阳性神经祖细胞（P-NPC）亚群中上调，显示出显著的增殖和进展特性，并可能激活G2M检查点途径。综合列线图预测1-，通过考虑P-NPC，GBM的2年和3年总生存概率，年龄,化疗和放疗评分。CCNA2和NEK2通过靶向细胞周期调节胶质母细胞瘤的进展，因此表明针对GBM中CCNA2和NEK2的新疗法的潜力。
