期刊论文详细信息
Frontiers in Oncology
Comprehensive Characterization of Alternative mRNA Splicing Events in Glioblastoma: Implications for Prognosis, Molecular Subtypes, and Immune Microenvironment Remodeling
Jiayue Zhang1  Liang Zhao1  Zhiyuan Liu1  Peng Zhao1  Yu Wang1  Shurui Xuan2 
[1] Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;
关键词: glioblastoma;    alternative splicing;    prognostic signature;    molecular classification;    immune microenvironment;   
DOI  :  10.3389/fonc.2020.555632
来源: DOAJ
【 摘 要 】

Alternative splicing (AS) of pre-mRNA has been widely reported to be associated with the progression of malignant tumors. However, a systematic investigation into the prognostic value of AS events in glioblastoma (GBM) is urgently required. The gene expression profile and matched AS events data of GBM patients were obtained from The Cancer Genome Atlas Project (TCGA) and TCGA SpliceSeq database, respectively. 775 AS events were identified as prognostic factors using univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) cox model was performed to narrow down candidate AS events, and a risk score model based on several AS events were developed subsequently. The risk score-based signature was proved as an efficient predictor of overall survival and was closely related to the tumor purity and immunosuppression in GBM. Combined similarity network fusion and consensus clustering (SNF-CC) analysis revealed two distinct GBM subtypes based on the prognostic AS events, and the associations between this novel molecular classification and clinicopathological factors, immune cell infiltration, as well as immunogenic features were further explored. We also constructed a regulatory network to depict the potential mechanisms that how prognostic splicing factors (SFs) regulate splicing patterns in GBM. Finally, a nomogram incorporating AS events signature and other clinical-relevant covariates was built for clinical application. This comprehensive analysis highlights the potential implications for predicting prognosis and clinical management in GBM.

【 授权许可】

Unknown   

  文献评价指标  
  下载次数:0次 浏览次数:0次