Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Research of Trauma Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Front Immunol. 2022 Jul 22;13:948630. doi: 10.3389/fimmu.2022.948630. eCollection 2022.
N1-methyladenosine (mA) is ubiquitous in eukaryotic RNA and regulates mRNA translation. However, little is known about its regulatory role in glioma. Here, we identified 4 mA modification-related patterns based on mA regulators in the TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) cohorts. The differences in survival prognosis between different clusters were striking. In addition, stemness, genomic heterogeneity, tumor microenvironment (TME), and immune cell infiltration were also significantly different between the poor and best prognostic clusters. To reveal the underlying mechanism, differentially expressed genes (DEGs) between the poor and best prognostic clusters were identified, and then were integrated for weighted correlation network analysis (WGCNA). After Univariate Cox-LASSO-Multivariate Cox analyses, DEGs PLEK2 and ABCC3 were screened as the risk-hub genes and were selected to construct an mA-related signature. Moreover, ABCC3 exacerbated glioma proliferation and was associated with temozolomide (TMZ) resistance. Overall, our study provided new insights into the function and potential therapeutic role of mA in glioma.
N1-甲基腺苷(mA)在真核 RNA 中普遍存在,可调节 mRNA 翻译。然而,mA 在神经胶质瘤中的调控作用知之甚少。在此,我们基于 TCGA(癌症基因组图谱)和 CGGA(中国脑胶质瘤基因组图谱)队列中的 mA 调节因子,鉴定了 4 种 mA 修饰相关模式。不同聚类之间的生存预后差异显著。此外,在预后不良和最佳预后聚类之间,干性、基因组异质性、肿瘤微环境(TME)和免疫细胞浸润也存在显著差异。为了揭示潜在的机制,我们鉴定了预后不良和最佳预后聚类之间的差异表达基因(DEGs),然后进行加权相关网络分析(WGCNA)的整合。经过单变量 Cox-LASSO-多变量 Cox 分析,筛选出差异表达基因 PLEK2 和 ABCC3 作为风险枢纽基因,并选择构建 mA 相关特征。此外,ABCC3 可加重神经胶质瘤的增殖,并与替莫唑胺(TMZ)耐药相关。总之,我们的研究为 mA 在神经胶质瘤中的功能和潜在治疗作用提供了新的见解。