Wang Zhi, Yuan Chi, Xu Tao, Xie Weixing, Wu Jiehua, Wang Hegui
Department of Cardiology, Huangshan Shoukang Hospital, Huangshan, China.
Department of Cardiology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Genet. 2025 Jul 2;16:1541342. doi: 10.3389/fgene.2025.1541342. eCollection 2025.
Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases associated with significant morbidity and mortality in patients with both conditions. The objective of this research is to enhance our understanding of the shared pathogenesis underlying the two diseases and to identify novel therapeutic targets.
Differentially expressed genes (DEGs) in heart failure and atrial fibrillation were obtained through the analysis and comparison of transcriptional expression profiles from the Gene Expression Omnibus (GEO) datasets. By integrating these datasets with the known ferroptosis-related genes (FRGs) from GeneCards and PubMed, we identified ferroptosis-related differentially expressed genes (FRDEGs). Functional enrichment and the construction of the PPI network for key genes were conducted. The mRNA-miRNA and mRNA-TF Regulatory Network were constructed via the ChIPBase and TarBase databases. Receiver operating characteristic (ROC) was utilized to screen out the FRDEGs and validate their diagnostic values. Gene expression levels were detected by qPCR in patient serum samples.
By analyzing the transcriptional expression profiles of the GEO datasets, , , , , and were identified as FRDEGs in AF and HF, which were revealed to be involved in iron ion transport, homeostasis, and oxidoreductase activity. Further insights from Gene Set Enrichment Analysis (GSEA) indicated that FRDEGs are primarily enriched in the IL-12 signaling pathway in HF and significantly enriched in the collagen assembly pathway in AF. The diagnostic efficacy of six genes in AF validation sets was good (AUC: 0.940, 0.920, 1.000, 0.960, 0.900, 0.960, as well as in the HF validation set (AUC: 0.842, 0.879, 0.865, 0.787, 0.812, 0.696).Utilizing the GOSemSim package, we conducted a functional similarity analysis on the five hub genes and discovered their significant roles in disease, ranked as follows: >>>>. qRT-PCR verified the expression differences of , , and .
Our findings provide a theoretical basis for the clinical diagnosis and treatment of AF and HF. These results provide valuable insights into potential biomarkers for diagnosis and targets for therapeutic intervention in AF and HF.
心房颤动（AF）和心力衰竭（HF）是常见的心血管疾病，在同时患有这两种疾病的患者中，具有较高的发病率和死亡率。本研究的目的是加深我们对这两种疾病共同发病机制的理解，并确定新的治疗靶点。
通过对基因表达综合数据库（GEO）数据集中转录表达谱的分析和比较，获得心力衰竭和心房颤动中差异表达基因（DEGs）。通过将这些数据集与来自基因卡片（GeneCards）和PubMed的已知铁死亡相关基因（FRGs）整合，我们确定了铁死亡相关差异表达基因（FRDEGs）。对关键基因进行功能富集分析并构建蛋白质-蛋白质相互作用（PPI）网络。通过ChIPBase和TarBase数据库构建mRNA- miRNA和mRNA-转录因子（TF）调控网络。利用受试者工作特征曲线（ROC）筛选出FRDEGs并验证其诊断价值。通过qPCR检测患者血清样本中的基因表达水平。
通过分析GEO数据集的转录表达谱，确定了 、 、 、 、 和 为AF和HF中的FRDEGs，这些基因被发现参与铁离子转运、稳态和氧化还原酶活性。基因集富集分析（GSEA）的进一步见解表明，FRDEGs在HF中主要富集于白细胞介素-12信号通路，在AF中显著富集于胶原蛋白组装通路。六个基因在AF验证集中的诊断效能良好（AUC：0.940、0.920、1.000、0.960、0.900、0.960），在HF验证集中也如此（AUC：0.842、0.879、0.865、0.787、0.812、0.696）。利用GOSemSim软件包，我们对五个枢纽基因进行了功能相似性分析，发现它们在疾病中具有重要作用，排名如下： >>>>。qRT-PCR验证了 、 和 的表达差异。
我们的研究结果为AF和HF的临床诊断和治疗提供了理论依据。这些结果为AF和HF的潜在诊断生物标志物和治疗干预靶点提供了有价值的见解。
