Yu Xiao, Zhang Xiaopeng, Bilal Hazrat, Shi Chang, Sun Lei
Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Department of Pathology, First Affiliated Hospital, Dalian, Liaoning Province, China.
Sci Rep. 2025 Feb 1;15(1):4012. doi: 10.1038/s41598-025-88568-2.
Current diagnostic biomarkers for acute myocardial infarction (AMI), such as troponins, often lack specificity, leading to false positives under non-cardiac conditions. Recent studies have implicated circadian rhythm and immune infiltration in the pathogenesis of AMI. This study hypothesizes that analyzing the interplay between circadian rhythm-related gene expression and immune infiltration identify highly specific diagnostic biomarkers for AMI. Our results demonstrated differential expression of 15 circadian rhythm-related genes (CRGs) between AMI patients and healthy individuals, with five key genes-JUN, NAMPT, S100A8, SERPINA1, and VCAN identified as key contributors to this process. Functional enrichment analyses suggest these genes significantly influence cytokine and chemokine production in immune responses. Immune infiltration assessments using ssGSEA indicated elevated levels of neutrophils, macrophages, and eosinophils in AMI patients. Additionally, we identified potential therapeutic implications with 13 pivotal miRNAs and 10 candidate drugs targeting these genes. The Benjamini-Hochberg method was employed to adjust for multiple testing, and the results retained statistical significance. RT-qPCR analysis further confirmed the upregulation of these five genes under hypoxic conditions, compared to controls. Collectively, our findings highlight the critical role of CRGs in AMI, providing a foundation for improved diagnostic approaches and novel therapeutic targets.
目前用于急性心肌梗死(AMI)的诊断生物标志物,如肌钙蛋白,往往缺乏特异性,导致在非心脏疾病情况下出现假阳性。最近的研究表明昼夜节律和免疫浸润参与了AMI的发病机制。本研究假设,分析昼夜节律相关基因表达与免疫浸润之间的相互作用,可识别出用于AMI的高特异性诊断生物标志物。我们的结果显示,AMI患者与健康个体之间有15个昼夜节律相关基因(CRGs)存在差异表达,其中5个关键基因——JUN、NAMPT、S100A8、SERPINA1和VCAN被确定为这一过程的关键促成因素。功能富集分析表明,这些基因在免疫反应中显著影响细胞因子和趋化因子的产生。使用单样本基因集富集分析(ssGSEA)进行的免疫浸润评估表明,AMI患者中性粒细胞、巨噬细胞和嗜酸性粒细胞水平升高。此外,我们确定了13个关键的微小RNA(miRNAs)和10种靶向这些基因的候选药物的潜在治疗意义。采用Benjamini-Hochberg方法对多重检验进行校正,结果仍具有统计学意义。与对照组相比,逆转录定量聚合酶链反应(RT-qPCR)分析进一步证实在缺氧条件下这5个基因的表达上调。总的来说,我们的研究结果突出了CRGs在AMI中的关键作用,为改进诊断方法和确定新的治疗靶点奠定了基础。