Liu Xuejing, Bai Yueting, Chen Han, Qian Nianfeng, Wu Lina, Zhao Li, Wang Shuo, Shen Chong, Jiang Hongqing
Department of Gynecology and Obstetrics, Haidian Maternal and Child Health Hospital, Beijing, China.
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Medicine (Baltimore). 2025 Mar 7;104(10):e41784. doi: 10.1097/MD.0000000000041784.
Pre-eclampsia (PE) is a multisystem pregnancy disorder characterized by placental and maternal endothelial dysfunction, and affects approximately 5% to 7% of pregnancies worldwide, leading to significant maternal and neonatal morbidity and mortality. Mounting evidence indicates that placental oxidative stress (OS) plays a critical role in the pathogenesis of PE. However, the specific mechanisms associated with OS during the occurrence and progression of PE remain largely unknown. Thus, we aimed to identify the key molecules associated with OS and explore their potential mechanisms in PE. Transcriptome data were downloaded from the Gene Expression Omnibus database, including 80 PE and 77 normal placental tissues. OS-related genes were identified using the Gene Ontology database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to analyze the functions and pathways of the OS-related differentially expressed genes (OS-DEGs). Protein-protein interaction networks were constructed using the Search Tool for the Retrieval of Interacting Genes database, and hub genes were screened using molecular complex detection and CytoHubba. Finally, the diagnostic value and drug-gene interactions of the hub genes were evaluated. We identified 470 differentially expressed genes and 43 OS-DEGs. These genes were mainly enriched in OS-related biological processes, the HIF-1 and MAPK signaling pathways. Furthermore, 5 hub genes were identified: VEGFA, CCL2, mitogen-activated protein kinase 8 (MAPK8), HMOX1, and Cytochrome B-245 Beta Chain (CYBB). CYBB and MAPK8 had the highest diagnostic accuracies, with area under the curve values of 0.767 and 0.764, respectively. We predicted 43 potentially targeted drugs for PE treatment. CYBB and MAPK8 may be valuable biomarkers that mediate OS through multiple pathways to promote the occurrence and development of PE. We conclude from our study that OS has involvement in PE, and improved our understanding of OS-related molecular pathways in the pathogenesis of PE.
子痫前期（PE）是一种多系统妊娠疾病，其特征为胎盘和母体血管内皮功能障碍，全球约5%至7%的妊娠会受其影响，导致严重的母婴发病和死亡。越来越多的证据表明，胎盘氧化应激（OS）在PE的发病机制中起关键作用。然而，PE发生和发展过程中与OS相关的具体机制仍 largely未知。因此，我们旨在识别与OS相关的关键分子，并探索它们在PE中的潜在机制。转录组数据从基因表达综合数据库下载，包括80例PE胎盘组织和77例正常胎盘组织。使用基因本体数据库识别OS相关基因。进行基因本体和京都基因与基因组百科全书富集分析，以分析OS相关差异表达基因（OS-DEGs）的功能和途径。使用检索相互作用基因的搜索工具数据库构建蛋白质-蛋白质相互作用网络，并使用分子复合物检测和CytoHubba筛选枢纽基因。最后，评估枢纽基因的诊断价值和药物-基因相互作用。我们识别出470个差异表达基因和43个OS-DEGs。这些基因主要富集于OS相关生物学过程、HIF-1和MAPK信号通路。此外，识别出5个枢纽基因：血管内皮生长因子A（VEGFA）、趋化因子配体2（CCL2）、丝裂原活化蛋白激酶8（MAPK8）、血红素加氧酶1（HMOX1）和细胞色素B-245β链（CYBB）。CYBB和MAPK8具有最高的诊断准确性，曲线下面积值分别为0.767和0.764。我们预测了43种可能用于PE治疗的靶向药物。CYBB和MAPK8可能是有价值的生物标志物，它们通过多种途径介导OS，促进PE的发生和发展。我们从研究中得出结论，OS参与了PE，并增进了我们对PE发病机制中OS相关分子途径的理解。
