通过综合生物信息学分析鉴定胶质瘤中枢基因和生物学途径

Lulu Chen, Tao Sun, Jian Li, Yongxuan Zhao
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引用次数: 1

摘要

目的胶质瘤是颅内最常见的原发性恶性肿瘤,但其发病机制尚不清楚。方法从基因表达综合数据库中整合4个符合条件的胶质瘤微阵列数据集,采用鲁棒秩聚集法鉴定胶质瘤样本与正常样本之间表达差异显著的基因(DEGs)。我们使用这些deg通过加权基因共表达网络分析来探索与胶质瘤生存密切相关的关键基因。然后,我们通过多个数据库构建了关键基因的预后和生存分析验证。我们还利用基因集富集分析(GSEA)和基因集变异分析(GSVA)探讨了它们潜在的生物学功能。结果我们选择了DLGAP5、CDCA8、NCAPH和CCNB2这四个在胶质瘤样本中异常上调的基因进行验证。他们表现出高水平的异柠檬酸脱氢酶基因突变和肿瘤分级,以及对胶质瘤的良好预后和诊断价值。它们的甲基化水平在胶质瘤样本中普遍较低。GSEA和GSVA分析表明,这些基因与胶质瘤的增殖密切相关。结论这些发现为胶质瘤的发病机制提供了新的认识。枢纽基因具有作为诊断和治疗标记物的潜力。
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Identification of hub genes and biological pathways in glioma via integrated bioinformatics analysis
Objective Glioma is the most common intracranial primary malignancy, but its pathogenesis remains unclear. Methods We integrated four eligible glioma microarray datasets from the gene expression omnibus database using the robust rank aggregation method to identify a group of significantly differently expressed genes (DEGs) between glioma and normal samples. We used these DEGs to explore key genes closely associated with glioma survival through weighted gene co-expression network analysis. We then constructed validations of prognosis and survival analyses for the key genes via multiple databases. We also explored their potential biological functions using gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). Results We selected DLGAP5, CDCA8, NCAPH, and CCNB2, as four genes that were abnormally up-regulated in glioma samples, for verification. They showed high levels of isocitrate dehydrogenase gene mutation and tumor grades, as well as good prognostic and diagnostic value for glioma. Their methylation levels were generally lower in glioma samples. GSEA and GSVA analyses suggested the genes were closely involved with glioma proliferation. Conclusion These findings provide new insights into the pathogenesis of glioma. The hub genes have the potential to be used as diagnostic and therapeutic markers.
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