Xing Yiming, Lin Xianhe
Cardiology Department, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
Sci Rep. 2025 Apr 30;15(1):15144. doi: 10.1038/s41598-025-99648-8.
Coronary artery disease (CAD), a widespread cardiovascular ailment, exhibits a strong association with palmitoylation. This research aimed to elucidate the role of S-palmitoylation in CAD through bioinformatics, providing novel perspectives on the mechanism underlying CAD. By intersecting differentially expressed genes with weighted gene co-expression network analysis (WGCNA) from the GSE113079 dataset, 534 differentially expressed palmitoylation-related genes (DE-PRGs) were identified. Protein-protein interaction (PPI) network analysis, in conjunction with machine learning algorithms and immune infiltration analysis utilizing CIBERSORT, identified CXCL12, KRTAP4-7, and PPP2R2B as pivotal hub genes in CAD progression with significant immune links. Enrichment analyses revealed their predominant roles in immune regulation. Nomogram and ROC curve analyses revealed robust diagnostic predictive capabilities grounded in the three hub genes. A regulatory network involving the transcription factor HDAC2 and miRNA hsa-mir-23a-3p was predicted. Single-cell sequencing (GSE121893) further highlighted endothelial cells, fibroblasts, and macrophages as central cellular interactors, with significant crosstalk among these populations. These findings positioned CXCL12, KRTAP4-7 and PPP2R2B as key palmitoylated hub genes in CAD, thereby offering dual potential as diagnostic markers and therapeutic targets.
冠状动脉疾病(CAD)是一种广泛存在的心血管疾病,与棕榈酰化密切相关。本研究旨在通过生物信息学阐明S-棕榈酰化在CAD中的作用,为CAD的潜在机制提供新的视角。通过将来自GSE113079数据集的差异表达基因与加权基因共表达网络分析(WGCNA)相结合,鉴定出534个差异表达的棕榈酰化相关基因(DE-PRGs)。蛋白质-蛋白质相互作用(PPI)网络分析,结合机器学习算法和利用CIBERSORT的免疫浸润分析,确定CXCL12、KRTAP4-7和PPP2R2B是CAD进展中的关键枢纽基因,具有显著的免疫联系。富集分析揭示了它们在免疫调节中的主要作用。列线图和ROC曲线分析显示,基于这三个枢纽基因具有强大的诊断预测能力。预测了一个涉及转录因子HDAC2和miRNA hsa-mir-23a-3p的调控网络。单细胞测序(GSE121893)进一步突出了内皮细胞、成纤维细胞和巨噬细胞是核心细胞相互作用因子,这些细胞群体之间存在显著的串扰。这些发现将CXCL12、KRTAP4-7和PPP2R2B定位为CAD中关键的棕榈酰化枢纽基因,从而提供了作为诊断标志物和治疗靶点的双重潜力。