Genome-Wide Analysis for the Regulation of Gene Alternative Splicing by DNA Methylation Level in Glioma and its Prognostic Implications

Frontiers in Genetics

Yihan Chen¹  Zhijie Han¹  Yijie He¹  Zeyuan Yang¹  Yaqin Tang¹  Lin Huang¹  Yue He²  Yongheng Wang³ 

[1] Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China;Group of Mathematics Education Teaching and Research, Chongqing Fudan Secondary School, Chongqing, China;International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, China;

关键词: glioma;    alternative splicing;    methylation modification;    clinical prognosis;    TCGA;   

DOI  :  10.3389/fgene.2022.799913

来源: DOAJ

【 摘 要 】

Glioma is a primary high malignant intracranial tumor with poorly understood molecular mechanisms. Previous studies found that both DNA methylation modification and gene alternative splicing (AS) play a key role in tumorigenesis of glioma, and there is an obvious regulatory relationship between them. However, to date, no comprehensive study has been performed to analyze the influence of DNA methylation level on gene AS in glioma on a genome-wide scale. Here, we performed this study by integrating DNA methylation, gene expression, AS, disease risk methylation at position, and clinical data from 537 low-grade glioma (LGG) and glioblastoma (GBM) individuals. We first conducted a differential analysis of AS events and DNA methylation positions between LGG and GBM subjects, respectively. Then, we evaluated the influence of differential methylation positions on differential AS events. Further, Fisher’s exact test was used to verify our findings and identify potential key genes in glioma. Finally, we performed a series of analyses to investigate influence of these genes on the clinical prognosis of glioma. In total, we identified 130 glioma-related genes whose AS significantly affected by DNA methylation level. Eleven of them play an important role in glioma prognosis. In short, these results will help to better understand the pathogenesis of glioma.

【 授权许可】

Unknown