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    不明原因复发性流产中铁死亡的生物信息学分析及验证

    Bioinformatic analysis and validation of ferroptosis in unexplained recurrent spontaneous abortion

      摘要
    • 摘要: 目的：探究铁死亡关键基因在不明原因复发性流产（URSA）发生发展中的作用，初步确定潜在生物标志物。方法：从基因表达综合（GEO）数据库下载数据集GSE26787，利用GEO2R 筛选差异表达基因（DEGs）；从FerrDb V2数据库下载铁死亡相关基因；DEGs与铁死亡基因取交集获得URSA 铁死亡相关基因；利用DAVID 数据库对URSA 铁死亡相关基因进行基因本体（GO）富集及京都基因与基因组百科全书（KEGG）通路分析；利用String数据库和Cytoscape软件分析蛋白互作网络，筛选Hub基因；采用实时荧光定量PCR（RT-qPCR）检测Hub 基因在人工流产组及URSA 组患者蜕膜组织中mRNA 的表达水平。结果：共筛选出55 个URSA 铁死亡基因；GO 功能富集提示URSA 铁死亡相关基因主要在自噬调节、RNA 聚合酶Ⅱ启动子转录正调控、膜的整体组分、酶及p53蛋白受体结合富集。KEGG通路分析显示URSA铁死亡基因富集最明显的为FoXO信号通路。采用String 数据库及Cytoscape 软件筛选出的URSA 铁死亡关键基因分别为EGFR、SRC、KRAS、MDM2。RT-qPCR 检测结果显示，EGFR、SRC、MDM2在URSA 组中的表达均低于人工流产组（均P< 0.05）；KRAS在URSA 组和人工流产组中表达无统计学差异（P> 0.05）。结论：铁死亡相关基因EGFR、SRC、MDM2可作为诊治URSA的潜在生物标志物。

       

      Abstract: Objective:To explore the the role of key genes of ferroptosis in the occurrence and development of unexplained recurrent spontaneous abortion(UR-SA), and to preliminarily identify the potential bio-markers.Methods:The GSE26787 data set was downloaded from Gene Expression Synthesis (GEO)database, and the differentially expressed genes(DEGs)were screened by GEO2R, obtaining ferroptosis-related genes from FerrDb V2 database.The ferroptosisrelated genes in URSA were obtained by intersection of DEGs and ferroptosis genes.The gene ontology(GO)en-richment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of ferroptosis-related genes in URSA were performed using DAVID database.The protein interaction network was analyzed using String data-base and Cytascape software to screen the Hub genes.Real-time fluorescence quantitative polymerase chain reac-tion(RT-qPCR)was used to detect the mRNA expression levels of Hub genes in the decidua tissues of patients in the induced abortion group and the URSA group.Results:A total of 55 ferroptosis-related genes in URSA were screened.GO functional enrichment analysis found that ferroptosis-related genes in URSA were mainly enriched in the regulation of macroautophagy, positive regulation of transcription from RNA polymerase Ⅱpromoter, inte-gral components of the membrane and enzyme and p53 receptor binding.The enrichment analysis of KEGG path-way showed that the most obvious enrichment of ferroptosis-related genes in URSA was the FoxO signaling path-way.String database and Cytoscape software were used to screen the key genes of ferroptosis EGFR、SRC、KRAS、MDM2 in URSA.The results of RT-qPCR showed that the expressions of EGFR, SRC and MDM2 in the URSA group were lower than those in the induced abortion group(all P< 0.05).There was no statistically signifi-cant difference in the expression of KRAS between URSA group and induced abortion group (P> 0.05).Conclusion: Ferroptosis-related genes EGFR, SRC and MDM2 can be used as potential biomarkers for diagnosis and treatment of URSA.

       

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