Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG)
Kunjian Lei,
Yilei Sheng,
Min Luo,
Junzhe Liu,
Chuandong Gong,
Shigang Lv,
Wei Tu,
Minhua Ye,
Miaojing Wu,
Bing xiao,
Hua Fang,
Haitao Luo,
Xinjun Liu,
Xiaoyan Long,
Xingen Zhu,
Kai Huang,
Jingying Li
Affiliations
Kunjian Lei
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; JXHC Key Laboratory of Neurological Medicine, Nanchang University, Nanchang, Jiangxi, China
Yilei Sheng
Jiangxi Provincial Key Laboratory of Nervous System Tumors and Cerebrovascular Diseases, Nanchang University, Nanchang, Jiangxi, China; JXHC Key Laboratory of Neurological Medicine, Nanchang University, Nanchang, Jiangxi, China; Nanchang University, Nanchang, Jiangxi, 330006, China
Min Luo
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi, 330006, China
Junzhe Liu
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi, 330006, China
Chuandong Gong
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi, 330006, China
Shigang Lv
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
Wei Tu
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
Minhua Ye
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
Miaojing Wu
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
Bing xiao
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
Hua Fang
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
Haitao Luo
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
Xinjun Liu
People's Hospital of Yingtan City, Jiangxi Province, Yingtan, Jiangxi, 335099, China
Xiaoyan Long
East China Institute of Digital Medical Engineering, Shangrao, Jiangxi, 334000, China
Xingen Zhu
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; JXHC Key Laboratory of Neurological Medicine, Nanchang University, Nanchang, Jiangxi, China
Kai Huang
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; JXHC Key Laboratory of Neurological Medicine, Nanchang University, Nanchang, Jiangxi, China
Jingying Li
Department of Comprehensive Intensive Care Unit, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China; Corresponding author.
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.
