Yang Zeyuan, He Yijie, Wang Yongheng, Huang Lin, Tang Yaqin, He Yue, Chen Yihan, Han Zhijie
Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China.
International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, China.
Front Genet. 2022 Mar 4;13:799913. doi: 10.3389/fgene.2022.799913. eCollection 2022.
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.
胶质瘤是一种原发性高恶性颅内肿瘤，其分子机制尚不清楚。先前的研究发现，DNA甲基化修饰和基因可变剪接（AS）在胶质瘤的肿瘤发生中都起着关键作用，并且它们之间存在明显的调控关系。然而，迄今为止，尚未进行全面的研究来在全基因组范围内分析DNA甲基化水平对胶质瘤中基因AS的影响。在此，我们通过整合来自537例低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）患者的DNA甲基化、基因表达、AS、疾病风险甲基化位点和临床数据来开展这项研究。我们首先分别对LGG和GBM患者之间的AS事件和DNA甲基化位点进行差异分析。然后，我们评估差异甲基化位点对差异AS事件的影响。此外，使用Fisher精确检验来验证我们的发现并鉴定胶质瘤中的潜在关键基因。最后，我们进行了一系列分析以研究这些基因对胶质瘤临床预后的影响。总共，我们鉴定出130个与胶质瘤相关的基因，其AS受DNA甲基化水平的显著影响。其中11个在胶质瘤预后中起重要作用。简而言之，这些结果将有助于更好地理解胶质瘤的发病机制。
