Li Can, Liu Fang, Li Chao, Zhao Xiangzhong, Lv Qiulan, Jiang Aiping, Zhao Shuping
Department of Obstetrics and Gynecology, Qingdao Women and Children's Hospital, Shandong University, Jinan, Shandong, China.
Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Front Immunol. 2025 Jul 17;16:1595706. doi: 10.3389/fimmu.2025.1595706. eCollection 2025.
Preeclampsia(PE) is closely linked to adverse maternal and fetal outcomes. Given the pivotal roles of mitochondria in various human diseases and the limited research on their involvement in PE, this study identified biomarkers linked to mitochondrial metabolism in PE and their roles in its pathogenesis. Data from three datasets were integrated using the ComBat algorithm to mitigate batch effects. Differential expression analysis identified genes differentially expressed between PE cases and Control group. Cross-referencing these genes with mitochondrial energy metabolism-related genes (MMRGs) isolated mitochondrial energy metabolism-related differentially expressed genes (MMRDEGs). GO and KEGG analysis were performed to elucidate the functions of the MMRDEGs. A diagnostic model using Random Forest and logistic regression was validated by ROC curve analysis. mRNA expressions of , , , and were quantified via qPCR. Immune characteristics were explored, and PPI, mRNA-miRNA, mRNA-TF and mRNA-RBP interaction networks were constructed. AlphaFold analyzed protein structures of , and A total of 1073 DEGs and 24 MMRDEGs were identified. , and formed the diagnostic model, which were predominantly enriched in pyruvate metabolism, glycolysis, and ATP metabolism pathways. CIBERSORT highlighted immune cell composition variations between PE and Control groups. , and exhibited increased mRNA expression levels in preeclamptic placentas. Therefore, MMRDEGs may play a critical role in the mechanism of oxidative stress and inflammatory response in PE by mediating metabolic regulation and immune modulation, potentially serving as diagnostic biomarkers associated with mitochondrial metabolism in preeclampsia.
子痫前期（PE）与不良母婴结局密切相关。鉴于线粒体在各种人类疾病中的关键作用以及关于其在PE中作用的研究有限，本研究确定了与PE中线粒体代谢相关的生物标志物及其在发病机制中的作用。使用ComBat算法整合来自三个数据集的数据以减轻批次效应。差异表达分析确定了PE病例与对照组之间差异表达的基因。将这些基因与线粒体能量代谢相关基因（MMRGs）进行交叉参照，分离出线粒体能量代谢相关差异表达基因（MMRDEGs）。进行GO和KEGG分析以阐明MMRDEGs的功能。通过ROC曲线分析验证了使用随机森林和逻辑回归的诊断模型。通过qPCR定量、、、和的mRNA表达。探索免疫特征，并构建PPI、mRNA-miRNA、mRNA-TF和mRNA-RBP相互作用网络。AlphaFold分析了、和的蛋白质结构。共鉴定出1073个差异表达基因（DEGs）和24个MMRDEGs。、和构成诊断模型，它们主要富集于丙酮酸代谢、糖酵解和ATP代谢途径。CIBERSORT突出了PE组和对照组之间免疫细胞组成的差异。、和在子痫前期胎盘组织中mRNA表达水平升高。因此，MMRDEGs可能通过介导代谢调节和免疫调节在PE的氧化应激和炎症反应机制中发挥关键作用，有可能作为子痫前期线粒体代谢相关的诊断生物标志物。
