Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala 695581, India.
Biomolecules. 2021 Mar 9;11(3):403. doi: 10.3390/biom11030403.
Anti- therapy is considered to be a useful therapeutic approach in many tumors, but the low efficacy and drug resistance limit its therapeutic potential and promote tumor growth through alternative mechanisms. We reanalyzed the gene expression data of xenografts of tumors of bevacizumab-resistant glioblastoma multiforme (GBM) patients, using bioinformatics tools, to understand the molecular mechanisms of this resistance. An analysis of the gene set data from three generations of xenografts, identified as 646, 873 and 1220, differentially expressed genes (DEGs) in the first, fourth and ninth generations, respectively, of the anti--resistant GBM cells. Gene Ontology (GO) and pathway enrichment analyses demonstrated that the DEGs were significantly enriched in biological processes such as angiogenesis, cell proliferation, cell migration, and apoptosis. The protein-protein interaction network and module analysis revealed 21 hub genes, which were enriched in cancer pathways, the cell cycle, the signaling pathway, and microRNAs in cancer. The pathway analysis revealed nine upregulated (, , , , , , , , and ) and five downregulated hub genes (, , , , and ) linked with several of the signaling pathway components. The survival analysis showed that three upregulated hub genes (, , and ) were associated with poor survival. The results predict that these hub genes associated with the GBM resistance to bevacizumab may be potential therapeutic targets or can be biomarkers of the anti- resistance of GBM.
抗疗法被认为是许多肿瘤中一种有用的治疗方法，但疗效低和耐药性限制了其治疗潜力，并通过替代机制促进肿瘤生长。我们使用生物信息学工具重新分析了贝伐单抗耐药性胶质母细胞瘤（GBM）患者异种移植物的基因表达数据，以了解这种耐药性的分子机制。对来自三代异种移植物的基因集数据的分析，分别鉴定了第一代、第四代和第九代抗耐药 GBM 细胞中的 646、873 和 1220 个差异表达基因（DEGs）。基因本体论（GO）和途径富集分析表明，DEGs 在血管生成、细胞增殖、细胞迁移和细胞凋亡等生物学过程中显著富集。蛋白质-蛋白质相互作用网络和模块分析揭示了 21 个枢纽基因，它们在癌症途径、细胞周期、信号通路和癌症中的 microRNAs 中富集。途径分析显示了九个上调的（、、、、、、、和）和五个下调的枢纽基因（、、、、和）与多个信号通路成分有关。生存分析表明，三个上调的枢纽基因（、和）与预后不良有关。这些结果预测，这些与贝伐单抗耐药性 GBM 相关的枢纽基因可能是潜在的治疗靶点，也可能是 GBM 抗耐药性的生物标志物。
