Yang Han, Wang Zhenwei, Xu Yawei, Du Yimei, Yang Haibo, Lu Yang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Sci Rep. 2025 Jan 2;15(1):319. doi: 10.1038/s41598-024-83455-8.
Necroptosis, a type of programmed cell death, has been increasingly linked to cardiovascular disease development, yet its role in dilated cardiomyopathy (DCM) remains unclear. In this study, we analyzed the GSE5406 dataset from the GEO database to explore necroptosis-related prognostic signatures in DCM using LASSO regression. We identified five necroptosis-related genes (BID, CAMK2B, GLUL, HSP90AB1, CHMP5) that define a necroptosis-related signature with strong predictive value, evidenced by ROC curve areas of 0.852 and 0.957 in training and test sets, respectively. Our analyses, including GO and GSEA enrichment, focused on pathways associated with high necroptosis-related scores (NRS) and revealed significant immune cell infiltration. Notably, nTreg and iTreg cells were enriched in the high NRS group, while CD8 naive T cells and CD8 T cells positively correlated with NRS. Small molecule drugs fenofibrate, procyclidine, and tienilic acid emerged as potential therapeutic agents for high-risk patients, with fenofibrate showing efficacy in inhibiting DCM progression in an inflammatory animal model. These findings underscore the clinical relevance of necroptosis-related genes in assessing DCM progression and prognosis and highlight their potential for targeted therapeutic development.
坏死性凋亡是一种程序性细胞死亡，越来越多地与心血管疾病的发展相关联，但其在扩张型心肌病（DCM）中的作用仍不清楚。在本研究中，我们分析了来自GEO数据库的GSE5406数据集，以使用LASSO回归探索DCM中与坏死性凋亡相关的预后特征。我们鉴定出五个与坏死性凋亡相关的基因（BID、CAMK2B、GLUL、HSP90AB1、CHMP5），它们定义了一个具有强大预测价值的与坏死性凋亡相关的特征，训练集和测试集的ROC曲线面积分别为0.852和0.957，证明了这一点。我们的分析，包括GO和GSEA富集分析，聚焦于与高坏死性凋亡相关评分（NRS）相关的通路，并揭示了显著的免疫细胞浸润。值得注意的是，nTreg和iTreg细胞在高NRS组中富集，而CD8幼稚T细胞和CD8 T细胞与NRS呈正相关。小分子药物非诺贝特、丙环定和替尼酸成为高危患者的潜在治疗药物，非诺贝特在炎症动物模型中显示出抑制DCM进展的功效。这些发现强调了与坏死性凋亡相关基因在评估DCM进展和预后方面的临床相关性，并突出了它们在靶向治疗开发中的潜力。
