Li Jie, Jiang Lingling, Kai Haili, Zhou Yang, Cao Jiachen, Tang Weichun
Department of Operating Room Nursing Group, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu, China.
Department of Gynaecology and Obstetrics, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu, China.
Sci Rep. 2025 Jan 8;15(1):1364. doi: 10.1038/s41598-025-85599-7.
Preeclampsia (PE) is a common hypertensive disease in women with pregnancy. With the development of bioinformatics, WGCNA was used to explore specific biomarkers to provide therapy targets efficiently. All samples were obtained from gene expression omnibus (GEO), then we used a package named "WGCNA" to construct a scale-free co-expression network and modules related to PE. Next, the search tool for the retrieval of interacting genes database (STRING) was adopted to structure the protein-protein interaction (PPI) of genes in the hub module. Furthermore, the MCODE plug-in was applied to discern hub clusters of the PPI network. We also utilized clusterprofiler to execute the functional analysis. Finally, hub genes were selected via Venn Plot and confirmed by quantitative real-time polymerase chain reaction. Through the co-expression networks and modules, we ensured the turquoise module was the most significant one related to PE. Functional analysis implied these genes were mainly enriched in the organic hydroxy compound metabolic process and Phosphatidylinositol signal system. Due to connectivity, the PPI network showed that GAPDH and VEGFA were the most conspicuous. Lastly, the Venn Plot screened eight hub genes (LDHA, ENG, OCRL, PIK3CB, FLT1, HK2, PKM, and LEP). LDHA was confirmed to be downregulated in PE tissues (P<0.001). This study revealed vital module and hub genes associated with preeclampsia and indicated that LDHA might be a therapeutic target in the future.
子痫前期（PE）是妊娠期女性常见的高血压疾病。随着生物信息学的发展，加权基因共表达网络分析（WGCNA）被用于探索特定生物标志物，以高效提供治疗靶点。所有样本均取自基因表达综合数据库（GEO），然后我们使用名为“WGCNA”的软件包构建了一个与子痫前期相关的无标度共表达网络和模块。接下来，采用检索相互作用基因数据库（STRING）的搜索工具构建枢纽模块中基因的蛋白质-蛋白质相互作用（PPI）。此外，应用MCODE插件识别PPI网络的枢纽簇。我们还利用clusterProfiler进行功能分析。最后，通过维恩图选择枢纽基因，并通过定量实时聚合酶链反应进行验证。通过共表达网络和模块，我们确定绿松石模块是与子痫前期最相关的模块。功能分析表明，这些基因主要富集于有机羟基化合物代谢过程和磷脂酰肌醇信号系统。基于连通性，PPI网络显示甘油醛-3-磷酸脱氢酶（GAPDH）和血管内皮生长因子A（VEGFA）最为显著。最后，维恩图筛选出8个枢纽基因（乳酸脱氢酶A（LDHA）、内皮糖蛋白（ENG）、肌醇多磷酸-5-磷酸酶L（OCRL）、磷脂酰肌醇-3-激酶催化亚基β（PIK3CB）、血管内皮生长因子受体1（FLT1）、己糖激酶2（HK2）、丙酮酸激酶M2型（PKM）和瘦素（LEP））。LDHA在子痫前期组织中被证实表达下调（P<0.001）。本研究揭示了与子痫前期相关的重要模块和枢纽基因，并表明LDHA可能是未来的一个治疗靶点。
