TEMEM45A在子痫前期胎盘组织中的表达及其临床意义

Expression and clinical significance of TMEM45A in placental tissues of preeclampsia

  • 摘要: 目的:探讨跨膜蛋白-45A(TMEM45A)在子痫前期(PE)的胎盘组织中的表达及其临床意义,并观察缺氧状态对于人绒毛膜滋养层细胞HTR-8/SV-NEO 中TMEM45A 表达的影响。方法:采用实时荧光定量PCR(RT-qPCR)检测PE 胎盘组织TMEM45A mRNA表达水平。采用western blotting和免疫组织化学(IHC)染色法检测PE胎盘组织TMEM45A蛋白表达水平,并分析TMEM45A表达水平与PE患者临床特征间的关系。构建HTR-8/SV-NEO细胞缺氧模型,探究缺氧对TMEM45A表达的影响。从基因表达综合数据库(GEO)中收集RNA-seq数据集及芯片数据,使用meta分析评估TMEM45A对PE的影响,绘制受试者工作特征(ROC)曲线,分析TMEM45A对PE的诊断效能。结果:PE胎盘组织TMEM45A mRNA及其蛋白表达均高于正常妊娠胎盘组织(P< 0.05)。TMEM45A蛋白低表达组与高表达组PE患者年龄、孕期增长的体重、孕次、产次、孕周、新生儿体重及尿蛋白、尿素氮(BUN)水平比较,差异均无统计学意义(均P> 0.05)。TMEM45A在HTR-8/SV-NEO缺氧细胞中的表达显著升高(P< 0.05)。Meta 分析显示:TMEM45A 表达为PE 的危险因素〔总SMD=1.23(0.31~2.14),I2=80.0%,P< 0.001〕。TMEM45A诊断PE的ROC曲线下面积(AUC)为0.788(95%CI:0.718~0.847,P< 0.001)。结论:TMEM45A在PE胎盘组织中呈高表达,对PE有一定的诊断价值;缺氧环境可导致滋养细胞的TMEM45A表达升高。

     

    Abstract: Objective:To investigate the expression and clinical significance of transmembrane protein-45A(TMEM45A) in placental tissues of preeclampsia (PE), and to observe the effect of hypoxia on the TMEM45A expression in human placental trophoblast HTR-8/SV-NEO.Methods:Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of TMEM45A mRNA in placental tissues of PE.Western blotting and immunohistochemical(IHC)staining were used to detect the expression level of TMEM45A protein in placental tissues of PE, and the relationship between the expression level of TMEM45A and the clinical manifestations of PE patients was analyzed.The hypoxia model of HTR-8/SV-NEO cells was constructed to explore the effect of hypoxia on the expression of TMEM45A.The RNA-seq dataset and chip data were collected from the Gene Expression Omnibus(GEO)database.Meta-analysis was used to evaluate the influence of TMEM45A on PE, and ROC curve was drawn to analyze the diagnostic ability of TMEM45A.Results:The expression of TMEM45A mRNA and protein in PE placental tissues were higher than those in normal pregnancy placental tissues (P< 0.05).There were no significant differences in age, weight gain during pregnancy, pregnancy time, delivery time, gestational week, neonatal weight, urinary protein and BUN levels between low expression group and high expression group (all P> 0.05).The expression of TMEM45A significantly increased in HTR-8/SV-NEO hypoxic cells(P< 0.05).Meta-analysis showed that TMEM45A was a risk factor for PETotal SMD=1.23 (0.31-2.14), I2=80.0%, P< 0.001.ROC curve analysis showed that TMEM45A had good diagnostic efficacy (AUC=0.788, CI: 0.718-0.847).Conclusion:TMEM45A is highly expressed in placental tissues of PE and has certain diagnostic value for PE.Hypoxic conditions can lead to an increase in TMEM45A expression in trophoblast cells.

     

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