Wang Xiaofeng, Xu Yichi, Dong Junpeng, Zhang Jinwen, Gu Wei, Qin Xiaoli
Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.
Hypertens Pregnancy. 2025 Dec;44(1):2542869. doi: 10.1080/10641955.2025.2542869. Epub 2025 Aug 8.
Abnormal hedgehog (Hh) signaling is linked to preeclampsia (PE). This study aimed to identify Hh-related diagnostic biomarkers for PE and assess the role of immune infiltration.
The PE dataset was obtained from GEO to screen DEGs. WGCNA was utilized to identify Hh pathway-related genes. Following the intersection of the two genes, key genes were screened by using LASSO, SVM-RFE, and RF. A model was constructed, with ROC applied for evaluating its performance. The ssGSEA was employed to analyze immune infiltration. Network Analyst was utilized to predict miRNA/TF targets.
Six Hh-related diagnostic genes were identified (SLC20A1, GPT2, PDK4, COASY, KRT81, CD163L1). The diagnostic model showed high accuracy (AUC > 0.8) in training and validation sets. PE patients exhibited immune dysfunction, including reduced dendritic cell, macrophage, and mast cell activity. Diagnostic genes strongly correlated with immune cells. Additionally, 25 miRNAs and 34 TFs potentially regulating these genes were predicted.
Six potential PE diagnostic biomarkers were identified, and their immune interactions were explored. This study enhances understanding of PE pathogenesis and suggests therapeutic targets.
异常的刺猬信号通路（Hh）与子痫前期（PE）相关。本研究旨在鉴定与Hh相关的PE诊断生物标志物，并评估免疫浸润的作用。
从基因表达综合数据库（GEO）获取PE数据集以筛选差异表达基因（DEG）。利用加权基因共表达网络分析（WGCNA）鉴定与Hh通路相关的基因。在这两组基因交集后，通过使用套索回归（LASSO）、支持向量机递归特征消除（SVM-RFE）和随机森林（RF）筛选关键基因。构建模型，并应用受试者工作特征曲线（ROC）评估其性能。采用单样本基因集富集分析（ssGSEA）分析免疫浸润。利用网络分析软件（Network Analyst）预测微小RNA（miRNA）/转录因子（TF）靶点。
鉴定出6个与Hh相关的诊断基因（溶质载体家族20成员1（SLC20A1）、谷丙转氨酶2（GPT2）、丙酮酸脱氢酶激酶4（PDK4）、辅酶A合成酶（COASY）、角蛋白81（KRT81）、CD163分子样1（CD163L1））。诊断模型在训练集和验证集中显示出高准确性（曲线下面积（AUC）>0.8）。PE患者表现出免疫功能障碍，包括树突状细胞、巨噬细胞和肥大细胞活性降低。诊断基因与免疫细胞密切相关。此外，预测了25个可能调节这些基因的miRNA和34个TF。
鉴定出6个潜在的PE诊断生物标志物，并探索了它们的免疫相互作用。本研究增进了对PE发病机制的理解，并提出了治疗靶点。
