Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; The Second Clinical Medicine College, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China.
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Exp Mol Pathol. 2021 Jun;120:104631. doi: 10.1016/j.yexmp.2021.104631. Epub 2021 Mar 17.
Preeclampsia is a life-threatening hypertensive disorder during pregnancy, while underlying pathogenesis and its diagnosis are incomplete.
In this study, we utilized the Robust Rank Aggregation method to integrate 6 eligible preeclampsia microarray datasets from Gene Expression Omnibus database. We used linear regression to assess the associations between significant differentially expressed genes (DEGs) and blood pressure. Functional annotation, protein-protein interaction, Gene Set Enrichment Analysis (GSEA) and single sample GSEA were employed for investigating underlying pathogenesis in preeclampsia.
We filtered 52 DEGs and further screened for 5 hub genes (leptin, pappalysin 2, endoglin, fms related receptor tyrosine kinase 1, tripartite motif containing 24) that were positively correlated with both systolic blood pressure and diastolic blood pressure. Receiver operating characteristic indicated that hub genes were potential biomarkers for diagnosis and prognosis in preeclampsia. GSEA for single hub gene revealed that they were all closely related to angiogenesis and estrogen response in preeclampsia. Moreover, single sample GSEA showed that the expression levels of 5 hub genes were correlated with those of immune cells in immunologic microenvironment at maternal-fetal interface.
These findings provide new insights into underlying pathogenesis in preeclampsia; 5 hub genes were identified as biomarkers for diagnosis and prognosis in preeclampsia.
子痫前期是一种危及生命的妊娠高血压疾病，但其发病机制和诊断尚不完全清楚。
本研究利用稳健秩聚合方法整合了来自基因表达综合数据库的 6 个合格的子痫前期微阵列数据集。我们使用线性回归来评估显著差异表达基因（DEGs）与血压之间的关联。功能注释、蛋白质-蛋白质相互作用、基因集富集分析（GSEA）和单样本 GSEA 用于研究子痫前期的潜在发病机制。
我们筛选出 52 个 DEGs，并进一步筛选出 5 个关键基因（瘦素、pappalysin 2、内胚层、fms 相关受体酪氨酸激酶 1、三结构域蛋白 24），这些基因与收缩压和舒张压均呈正相关。接受者操作特征表明，关键基因是子痫前期诊断和预后的潜在生物标志物。单基因 GSEA 表明，它们都与子痫前期的血管生成和雌激素反应密切相关。此外，单样本 GSEA 显示，5 个关键基因的表达水平与母胎界面免疫微环境中免疫细胞的表达水平相关。
这些发现为子痫前期的发病机制提供了新的见解；5 个关键基因被确定为子痫前期诊断和预后的生物标志物。
