生长分化因子15与子痫前期的关联Meta分析

Meta Analysis to Explore the Association between Growth Differentiation Factor 15 and Preeclampsia

目的:分析子痫前期(PE)患者各组织中生长分化因子15(GDF-15)的表达水平,为子痫前期发病机制和生物标志物的研究提供依据。方法:从基因表达综合(GEO)数据库下载子痫前期患者和正常对照孕妇胎盘组织的GDF15mRNA表达数据,同时通过检索PubMed、Google Scholar、Embase、Web of Science等数据库纳入子痫前期和GDF-15的相关英文文献,检索日期均截止到2022年8月10日。使用STATA软件对搜集到的数据进行Meta分析。结果:从GEO数据库中共检索出23个数据集,共包含269例子痫前期患者和392名正常孕妇;另有6篇符合标准的文献被纳入,包含331例子痫前期患者和2245名健康对照者。Meta分析结果显示,GDF-15 mRNA和GDF-15蛋白在子痫前期患者和正常孕妇中的表达水平与正常孕妇比较,差异无统计学意义(P>0.05),其标准化均数差(SMD)和95%置信区间(CI)分别为0.25(-0.12,0.63)和0.23(-0.18,0.64)。通过对样本采集时间进行亚组分析后发现,子痫前期患者孕中期GDF-15蛋白的表达水平较高[SMD(95%CI)为0.40(0.16,0.63)],而孕晚期的GDF-15 mRNA的升高与子痫前期发病风险呈正相关[SMD(95%CI)为0.56(0.09,1.03)]。结论:该研究结果表明GDF-15或不能成为子痫前期的预测或诊断标志物,仍需要其他的研究来进一步探究GDF-15与子痫前期的关联。

OBJECTIVE To analyze the expression of growth differentiation factor 15(GDF-15)in blood and placental tissues of patients with preeclampsia(PE)and to provide bioinformatics evidence for further studies on the pathogenesis and biomarkers of PE.METGDF-15 mRNA expression data from placental tissues of PE patients and normal control pregnant women were downloaded from the GEO database,while relevant literature on PE and GDF-15 were included by searching PubMed,Google Scholar,Embase,Web of Science.Then,Meta-analysis was performed by using STATA software.RESULTS Twenty-three datasets containing269 PE and 392 normal pregnant women were retrieved from the GEO databases,while another 6 papers containing 331 PE patients and 2245 healthy controls were included.GDF-15 mRNA and GDF-15 protein were not statistically different in PE patients compared to normal pregnant women,with standardized mean difference(SMD)and its 95%CI of 0.25(-0.12,0.63)and 0.23(-0.18,0.64),respectively.A subgroup analysis of sample collection time revealed that GDF-15 protein expression in the second trimester was higher in PE patients compared with controls[SMD(95%CI)=0.40(0.16,0.63)],while elevated GDF-15 mRNA in the third trimester was positively related with the risk of developing PE[SMD(95%CI)=0.56(0.09,1.03)].CONCLUSION The current study suggests that GDF-15 may not be a predictive or diagnostic marker for PE,and additional studies are still needed to explore the association of GDF-15 with PE.