目的:通过生物信息学方法探索盆腔器官脱垂(pelvic organ prolapse, POP)进展的关键基因和信号通路。方法:自公共数据库GEO下载数据集GSE12852和GSE28600,通过在线工具GEO2R分析获取差异基因,通过DAVID数据库进行GO和KEGG分析,通过STRING数据库分析制作基因之间PPI网络。收集子宫脱垂及非子宫脱垂的骶韧带组织各4例,通过免疫组化检测KRT5、KRT19、CLDN7、CLDN4在骶韧带组织中的表达。结果:两个数据集的差异基因经交集后,共有53个基因在POP患者的骶韧带中低表达。GO和KEGG分析发现,低表达基因与细胞外基质成分、细胞间连接等功能或通路相关。在PPI网络上,KRT5、KRT19、CLDN7、CLDN4基因可能在POP进展起到关键作用。免疫组化实验证实KRT5、KRT19、CLDN7、CLDN4蛋白水平在POP骶韧带中表达下调。结论:通过芯片数据的生物信息学分析与实验验证,筛选了与POP密切相关的基因和通路,其中KRT5、KRT19、CLDN7、CLDN4可能在POP的进展发挥重要作用。
Objective: To explore the key genes and signaling pathways in the progression of pelvic organ prolapse (POP) by bioinformatics analysis. Methods: The data sets GSE12852 and GSE28600 were downloaded from the public database GEO. The differential genes were obtained by online tool GEO2R analysis, GO and KEGG analysis were performed by DAVID database, and PPI network between genes was analyzed by STRING database. The expression of KRT5, KRT19, CLDN7 and CLDN4 in uterosacral ligament tissues was detected by immunohistochemistry. Results: After the intersection of the differential genes of the two data sets, a total of 53 genes were lowly expressed in the sacral ligament of POP patients. GO and KEGG analysis showed that low expression genes were related to functions or pathways such as extracellular matrix components and intercellular connections. On the PPI network, KRT5, KRT19, CLDN7, and CLDN4 genes might play a key role in POP progression. Immunohistochemical experiments confirmed that the protein levels of KRT5, KRT19, CLDN7 and CLDN4 were down-regulated in the sacral ligament of POP. Conclusion: These microarray data and bioinformatics analyses provide a useful method for the identification of key genes and pathways associated with POP. Moreover, some crucial DEGs, such as KRT5, KRT19, CLDN7, CLDN4, potentially play an important role in the development and progression of POP.
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