■WEE1是DNA损伤反应途径中的关键激酶,已被证明可有效治疗浆液性子宫癌。然而,它在神经胶质瘤中的作用,特别是低级别胶质瘤(LGG),尚不清楚。DNA甲基化对神经胶质瘤中WEE1表达的影响及其与免疫景观的相关性也需要进一步研究。
■这项研究使用了来自癌症基因组图谱(TCGA)的数据,中国胶质瘤基因组图谱(CGGA),和基因表达综合(GEO),并利用各种生物信息学工具来分析基因表达,生存,基因相关性,免疫评分,免疫浸润,基因组改变,肿瘤突变负荷,微卫星不稳定,胶质瘤患者的临床特征,WEE1DNA甲基化,预后分析,胶质瘤组织样本中的单细胞基因表达分布,和基于WEE1表达的免疫治疗反应预测。
■WEE1在LGG和胶质母细胞瘤(GBM)中上调,但与其他癌症相比,它对LGG的预后影响更大。高WEE1表达与LGG预后较差相关,特别是当与野生型IDH组合时。WEE1抑制剂MK-1775有效抑制LGG细胞系的增殖和迁移,对WEE1抑制更敏感。DNA甲基化负调控WEE1,且WEE1的高DNA高甲基化与LGG比GBM更好的预后相关。结合WEE1抑制和DNA甲基转移酶抑制显示出协同作用。此外,WEE1下调对免疫治疗反应具有良好的预测价值.共表达网络分析确定了参与WEE1介导的免疫景观调节的关键基因,分化,和LGG转移。
■我们的研究表明,WEE1是靶向治疗和预后评估的有希望的指标。值得注意的是,在LGG和GBM之间观察到WEE1的作用存在显着差异。对WEE1抑制的进一步研究,与DNA甲基转移酶抑制或免疫疗法联合使用,在LGG的背景下是有保证的。
UNASSIGNED: WEE1 is a critical kinase in the DNA damage response pathway and has been shown to be effective in treating serous uterine cancer. However, its role in gliomas, specifically low-grade glioma (LGG), remains unclear. The impact of DNA methylation on WEE1 expression and its correlation with the immune landscape in gliomas also need further investigation.
UNASSIGNED: This study used data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) and utilized various bioinformatics tools to analyze gene expression, survival, gene correlation, immune score, immune infiltration, genomic alterations, tumor mutation burden, microsatellite instability, clinical characteristics of glioma patients, WEE1 DNA methylation, prognostic analysis, single-cell gene expression distribution in glioma tissue samples, and immunotherapy response prediction based on WEE1 expression.
UNASSIGNED: WEE1 was upregulated in LGG and glioblastoma (GBM), but it had a more significant prognostic impact in LGG compared to other cancers. High WEE1 expression was associated with poorer prognosis in LGG, particularly when combined with wild-type IDH. The WEE1 inhibitor MK-1775 effectively inhibited the proliferation and migration of LGG cell lines, which were more sensitive to WEE1 inhibition. DNA methylation negatively regulated WEE1, and high DNA hypermethylation of WEE1 was associated with better prognosis in LGG than in GBM. Combining WEE1 inhibition and DNA methyltransferase inhibition showed a synergistic effect. Additionally, downregulation of WEE1 had favorable predictive value in immunotherapy response. Co-expression network analysis identified key genes involved in WEE1-mediated regulation of immune landscape, differentiation, and metastasis in LGG.
UNASSIGNED: Our study shows that WEE1 is a promising indicator for targeted therapy and prognosis evaluation. Notably, significant differences were observed in the role of WEE1 between LGG and GBM. Further investigation into WEE1 inhibition, either in combination with DNA methyltransferase inhibition or immunotherapy, is warranted in the context of LGG.