Tu Jiang-Lie, Fang Rui-Xue
Department of Obstetrics and Gynecology, The Affiliated Hospital of Guizhou Medical University, Guizhou Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guiyang, Guizhou, China.
Department of Emergency, Yueqing Fifth People's Hospital, Wenzhou, Zhejiang, China.
Front Med (Lausanne). 2025 Apr 17;12:1529074. doi: 10.3389/fmed.2025.1529074. eCollection 2025.
Fatty acid metabolism plays a major role in several inflammatory diseases such as endometriosis. However, its specific mechanism in endometriosis remains unclear. Therefore, this study aimed to investigate the hub genes involved in endometriosis and fatty acid metabolism using bioinformatics analyses.
The R package sva was used to remove batch effects from the GSE120103 and GSE25628 datasets, resulting in the creation of a combined GEO dataset. Differential analysis of the combined GEO dataset was interposed with fatty acid metabolism-related genes. Differentially expressed genes associated with fatty acid metabolism (FAMRDEGs) were subsequently identified. Functional enrichment analyses were performed using the clusterProfiler package, whereas gene set enrichment analysis (GSEA) was used to identify significant pathways. Protein-protein interaction (PPI) networks were constructed using STRING and visualized using Cytoscape to identify hub genes. Moreover, regulatory networks involving transcription factors and microRNAs were constructed using ChIPBase and ENCORI databases, respectively. Hub genes were validated via expression comparison and receiver operating characteristic curve analysis.
We identified 405 DEGs in the combined dataset, including 168 and 237 with upregulated and downregulated expression, respectively. Of these, 17 were FAMRDEGs. These genes were significantly involved in arachidonic acid and fatty acid metabolic processes. GSEA highlighted pathways such as Hamai_apoptosis_via_trail_dn for genes whose expression was downregulated, along with nuclear receptors in lipid metabolism and toxicity for genes with upregulated expression. The PPI network identified six hub genes: , and . showed the strongest positive correlation with immune cell effector memory CD8 T cells, whereas showed the strongest negative correlation with immune cell-activated CD8 T cells.
The identified hub genes may be potential biomarkers of fatty acid metabolism in endometriosis. This reveals the potential molecular mechanisms underlying this metabolic process and identifies therapeutic targets for future interventions.
脂肪酸代谢在子宫内膜异位症等多种炎症性疾病中起主要作用。然而，其在子宫内膜异位症中的具体机制仍不清楚。因此，本研究旨在通过生物信息学分析来研究参与子宫内膜异位症和脂肪酸代谢的关键基因。
使用R包sva去除GSE120103和GSE25628数据集的批次效应，从而创建一个合并的GEO数据集。对合并的GEO数据集进行差异分析，并与脂肪酸代谢相关基因进行比对。随后鉴定出与脂肪酸代谢相关的差异表达基因（FAMRDEGs）。使用clusterProfiler包进行功能富集分析，而基因集富集分析（GSEA）用于识别显著通路。使用STRING构建蛋白质-蛋白质相互作用（PPI）网络，并使用Cytoscape进行可视化以识别关键基因。此外，分别使用ChIPBase和ENCORI数据库构建涉及转录因子和 microRNA的调控网络。通过表达比较和受试者工作特征曲线分析对关键基因进行验证。
我们在合并数据集中鉴定出405个差异表达基因，其中分别有168个和237个基因表达上调和下调。其中，17个为FAMRDEGs。这些基因显著参与花生四烯酸和脂肪酸代谢过程。GSEA突出显示了一些通路，例如对于表达下调的基因有Hamai_apoptosis_via_trail_dn通路，以及对于表达上调的基因有脂质代谢和毒性中的核受体通路。PPI网络鉴定出六个关键基因： 、 和 。 与免疫细胞效应记忆CD8 T细胞显示出最强的正相关，而 与免疫细胞活化的CD8 T细胞显示出最强的负相关。
鉴定出的关键基因可能是子宫内膜异位症中脂肪酸代谢的潜在生物标志物。这揭示了该代谢过程潜在的分子机制，并确定了未来干预的治疗靶点。
