基于生物信息学途径研究CLDN4基因在卵巢癌中的作用及机制

Functional mechanism of CLDN4 gene in ovarian cancer based on bioinformatics approach

目的 基于生物信息学途径,研究紧密连接蛋白4(CLDN4)在卵巢癌中的作用机制。方法 从GEO数据库获取含有12个卵巢癌组织和正常组织的基因芯片,结合Oncomine数据库进行CLDN4 mRNA表达差异分析,筛选出差异基因109个,利用Cytoscape 3.8.2软件进行GO富集和KEGG富集分析,String数据库进行蛋白相互作用网络分析,找到关键节点蛋白16个,选取差异最大的CLDN4基因进行深入探讨,进行表达分析和GeneMANIA功能预测。结果 筛选109个差异基因进行GO富集和KEGG信号通路分析,发现参与Wnt/β-catenin、MAPK、MEK-ERK等信号通路;构建功能模块,找到关键蛋白16个,其中CLDN4 mRNA在卵巢癌中高表达,CLDN4表达与临床分期和生存状态有相关性;预测CLDN4基因在功能上与顶端连接复合体、细胞-细胞连接、内皮屏障的建立、内皮细胞发育与分化等有关。结论 CLDN4在卵巢癌中高表达,在癌细胞的增殖、转移中有一定作用,有望成为诊断和治疗卵巢癌的新生物标记物。

Objective To study the functional mechanism of closed protein 4(CLDN4) in ovarian cancer based on bioinformatics approach.Methods Gene chips containing 12 ovarian cancer tissues and normal tissues were obtained from GEO database, and CLDN4 mRNA expression difference was analyzed by Oncomine database.A total of 109 differential genes were screened out, and Cytoscape 3.8.2 software was used for GO enrichment and KEGG enrichment analysis.Protein interaction network analysis was conducted in String database, and 16 key node proteins were found.Among them, CLDN4 gene with the greatest difference was selected for in-depth discussion, and expression analysis and GeneMANIA function prediction were conducted.Results A total of 109 differential genes were screened for GO enrichment and KEGG signaling pathway analysis, which were found to be involved in Wnt/β-catenin, MAPK,MEK-ERK and other signaling pathways.Sixteen key proteins were found by building functional modules.CLDN4 mRNA was highly expressed in ovarian cancer, and CLDN4 expression was correlated with clinical stage and survival status.CLDN4 gene was predicted to be involved in apical junction complex, cell-cell connection, endothelial barrier establishment, endothelial cell development and differentiation.Conclusion CLDN4 is highly expressed in ovarian cancer and plays a role in the proliferation and metastasis of cancer cells, which is expected to be a new biomarker for the diagnosis and treatment of ovarian cancer.