Zhang M, Luo S C
Oncology Department, Sichuan Provincial Hospital and Sichuan Academy of Medical Science, Chengdu, Sichuan, China.
Genet Mol Res. 2016 Jan 22;15(1):gmr7496. doi: 10.4238/gmr.15017496.
The aim of this study is to analyze gene expression data to identify key genes and pathways associated with resistance to platinum-based chemotherapy in epithelial ovarian cancer (EOC) and to improve clinical treatment strategies. The gene expression data set was downloaded from Gene Expression Omnibus and included 12 chemotherapy-resistant EOC samples and 16 chemotherapy-sensitive EOC samples. A differential analysis was performed to screen out differentially expressed genes (DEGs). A functional enrichment analysis was conducted for the DEGs using the database for annotation, visualization, and integration discovery. A protein-protein interaction (PPI) network was constructed with information from the human protein reference database. Pathway-pathway interactions were determined with a test based on the hypergeometric distribution. A total of 1564 DEGs were identified in chemotherapy-sensitive EOC, including 654 upregulated genes and 910 downregulated genes. The top three upregulated genes were HIST1H3G, AKT3, and RTN3, while the top three downregulated genes were NBLA00301, TRIM62, and EPHA5. A Gene Ontology enrichment analysis showed that cell adhesion, biological adhesion, and intracellular signaling cascades were significantly enriched in the DEGs. A KEGG pathway enrichment analysis revealed that the calcium, mitogen-activated protein kinase, and B cell receptor signaling pathways were significantly over-represented in the DEGs. A PPI network containing 101 interactions was acquired. The top three hub genes were RAC1, CAV1, and BCL2. Five modules were identified from the PPI network. Taken together, these findings could advance the understanding of the molecular mechanisms underlying intrinsic chemotherapy resistance in EOC.
本研究的目的是分析基因表达数据,以识别与上皮性卵巢癌(EOC)铂类化疗耐药相关的关键基因和通路,并改进临床治疗策略。基因表达数据集从基因表达综合数据库下载,包括12个化疗耐药的EOC样本和16个化疗敏感的EOC样本。进行差异分析以筛选出差异表达基因(DEG)。使用注释、可视化和整合发现数据库对DEG进行功能富集分析。利用人类蛋白质参考数据库的信息构建蛋白质-蛋白质相互作用(PPI)网络。通过基于超几何分布的检验确定通路-通路相互作用。在化疗敏感的EOC中总共鉴定出1564个DEG,包括654个上调基因和910个下调基因。上调程度最高的三个基因是HIST1H3G、AKT3和RTN3,而下调程度最高的三个基因是NBLA00301、TRIM62和EPHA5。基因本体富集分析表明,细胞黏附、生物黏附和细胞内信号级联在DEG中显著富集。KEGG通路富集分析显示,钙、丝裂原活化蛋白激酶和B细胞受体信号通路在DEG中显著富集。获得了一个包含101个相互作用的PPI网络。前三个枢纽基因是RAC1、CAV1和BCL2。从PPI网络中识别出五个模块。综上所述,这些发现可以促进对EOC内在化疗耐药分子机制的理解。