Comprehensive analyses indicated the association between m6A related long non-coding RNAs and various pathways in glioma

被引:5
作者
Chen, Zhuohui [1 ]
Zhang, Wei [2 ]
Yan, Zhouyi [1 ]
Zhang, Mengqi [1 ,3 ]
机构
[1] Cent South Univ, Xiangya Hosp, Dept Neurol, 87 Xiangya Rd, Changsha 410008, Peoples R China
[2] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China
[3] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China
基金
中国国家自然科学基金;
关键词
glioma; immunotherapy sensitivity; m6A related lncRNA; prognosis prediction; tumor microenvironment; tumor mutation burden; NIVOLUMAB PLUS IPILIMUMAB; EXPANDED-ACCESS PROGRAM; TUMOR MUTATIONAL BURDEN; METHYLATION; EXPRESSION; PROGRESSION; REVEALS; CELLS; ENRICHMENT; REGULATORS;
D O I
10.1002/cam4.4913
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Glioma is one of the most malignant brain tumors and diseases. N6-methyladenosine modification (m6A) is the most abundant and prevalent internal chemical modification of mRNA and long non-coding RNAs (lncRNAs) in eukaryotes. Nevertheless, the correlated pathways and clinical utilization of m6A-related lncRNAs have not been fully evaluated in glioma. Methods Public RNA-sequencing and clinical annotation data were retrieved from TCGA, CGGA and GEO database. Differential expression analysis and univariate Cox regression analysis were performed to identify the m6A-related and differentially expressed lncRNAs with prognostic function (m6A-DELPF). The consensus clustering was performed to identify the expression pattern of m6A-DELPF. LASSO Cox regression analysis was performed to construct the lncRNA-based signature. The CIBERSORT and ESTIMATE algorithms were performed to analyze immune infiltration and tumor microenvironment, respectively. Immunotherapy sensitivity analysis was performed using data from TCIA. The small molecule drugs prediction analysis was performed using The Connectivity Map (CMap) database and STITCH database. A competing endogenous RNAs (ceRNA) network was constructed based on miRcode, miRDB, miRTarBase, TargetScan database. Results Two clusters (cluster1 and cluster2) were identified after unsupervised cluster analysis based on m6A-DELPF. Additionally, a 15-gene prognostic signature namely m6A-DELPFS was constructed. Analyses of epithelial-mesenchymal-transition score, tumor microenvironment, immune infiltration, clinical characterization analysis, and putative drug prediction were performed to confirm the clinical utility and efficacy of m6A-DELPFS. The potential mechanisms including tumor immune microenvironment of m6A-DELPF influence the initiation and progression of glioma. A clinically accessible nomogram was also constructed based on the m6A-DELPF and other survival-relevant clinical parameters. Two miRNAs and 114 mRNAs were identified as the downstream of seven m6A-related lncRNAs in a ceRNA network. Conclusion Our present research confirmed the clinical value of m6A related lncRNAs and their high correlation with tumor immunity, tumor microenvironment, tumor mutation burden and drug sensitivity in glioma.
引用
收藏
页码:760 / 788
页数:29
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