Lei Kunjian, Sheng Yilei, Luo Min, Liu Junzhe, Gong Chuandong, Lv Shigang, Tu Wei, Ye Minhua, Wu Miaojing, Xiao Bing, Fang Hua, Luo Haitao, Liu Xinjun, Long Xiaoyan, Zhu Xingen, Huang Kai, Li Jingying
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
Jiangxi Provincial Key Laboratory of Nervous System Tumors and Cerebrovascular Diseases, Nanchang University, Nanchang, Jiangxi, China.
Heliyon. 2024 Mar 7;10(6):e27510. doi: 10.1016/j.heliyon.2024.e27510. eCollection 2024 Mar 30.
N1-methyladenosine (m1A) modification is a crucial post-transcriptional regulatory mechanism of messenger RNA (mRNA) in living organisms. Few studies have focused on analysis of m1A regulators in lower-grade gliomas (LGG). We employed the Nonnegative Matrix Factorization (NMF) technique on The Cancer Genome Atlas (TCGA) dataset to categorize LGG patients into 2 groups. These groups exhibited substantial disparities in terms of both overall survival (OS) and levels of infiltrating immune cells. We collected the significantly differentially expressed immune-related genes between the 2 clusters, and performed LASSO regression analysis to obtain m1AScores, and established an m1A-related immune-related gene signature (m1A-RIGS). Next, we categorized all patients with LGG into high- and low-risk subgroups, predictive significance of m1AScore was confirmed by conducting univariate/multivariate Cox regression analyses. Additionally, we confirmed variations in immune-related cells and ssGSEA and among the high-/low-risk subcategories in the TCGA dataset. Finally, our study characterized the effects of MSR1 and BIRC5 on LGG cells utilizing Edu assay and flow cytometry to explore the effects of modulation of these genes on glioma. The results of this study suggested that m1A-RIGS may be an excellent prognostic indicator for patients with LGG, and could also promote development of novel immune-based treatment strategies for LGG. Additionally, BIRC5 and MSR1 may be potential therapeutic targets for LGG.
N1-甲基腺苷(m1A)修饰是生物体中信使核糖核酸(mRNA)的一种关键转录后调控机制。很少有研究聚焦于低级别胶质瘤(LGG)中m1A调控因子的分析。我们在癌症基因组图谱(TCGA)数据集上采用非负矩阵分解(NMF)技术,将LGG患者分为两组。这两组在总生存期(OS)和浸润免疫细胞水平方面均表现出显著差异。我们收集了这两个聚类之间显著差异表达的免疫相关基因,进行套索回归分析以获得m1A评分,并建立了一个与m1A相关的免疫相关基因特征(m1A-RIGS)。接下来,我们将所有LGG患者分为高风险和低风险亚组,通过进行单变量/多变量Cox回归分析证实了m1A评分的预测意义。此外,我们在TCGA数据集中证实了免疫相关细胞和单样本基因集富集分析(ssGSEA)在高/低风险亚组之间的差异。最后,我们的研究利用Edu检测和流式细胞术表征了MSR1和BIRC5对LGG细胞的影响,以探索这些基因的调控对胶质瘤的影响。本研究结果表明,m1A-RIGS可能是LGG患者的一个优秀预后指标,也可能促进LGG新型免疫治疗策略的发展。此外,BIRC5和MSR1可能是LGG的潜在治疗靶点。