Xu Cuixiang, Zhao Xiangrong, Li Huiting, Li Yaping, Feng Yangmeng, Zhang Guoan, Huang Xiaoyan
Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, Xi'an, People's Republic of China.
Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, Xi'an, People's Republic of China.
J Inflamm Res. 2025 May 15;18:6331-6345. doi: 10.2147/JIR.S498496. eCollection 2025.
RNA modifications are associated to various human diseases. However, the functions of RNA modification-related genes have yet to be thoroughly investigated in dilated cardiomyopathy (DCM). This study sought to conduct a comprehensive analysis of RNA modification-associated genes for the diagnosis and subtype classification of DCM.
We collected DCM and control sample RNA modification-related genes from Gene Expression Omnibus (GEO) microarray datasets. Differential expression analysis was performed on these using the "Limma" package in R. Univariate logistic regression, and the LASSO algorithm were used to identify optimal genes for diagnostic model establishment. Furthermore, ConsensusClusterPlus was used to identify RNA modification-molecular subtypes. Lastly, the expression of the hub RNA modification-related genes and their connection to DCM were confirmed using the clinical samples and mouse models.
Twenty-six RNA modification-related genes were identified as dysregulated in DCM, with strong connections noted among these genes. A diagnostic model based on 13 genes (, and ) with an AUC of 0.980 predicted DCM well. Infiltrating plasma B cells, eosinophils, CD8 T cells, and regulatory T cells correlated strongly with , and . Two RNA modification-molecular subtypes (clusters 1 and 2) were identified. Cluster 1 had greater RNA modification scores, lower immune ratings, and lower HLA-DRB1 and HLA-DPB1 expression than Cluster 2. Cluster 2 engaged metabolism-related pathways, while Cluster 1 activated renin-angiotensin system pathways.We further found a substantial link between lower cardiac function and up-regulation of , and down-regulation of in the 13 hub RNA modification-related genes.
In conclusion, our RNA modification-related diagnostic model predicts DCM well. The discovery of two RNA modification-molecular subgroups and four key pivotal genes may assist stratify DCM patients by risk.
RNA修饰与多种人类疾病相关。然而，RNA修饰相关基因在扩张型心肌病（DCM）中的功能尚未得到充分研究。本研究旨在对RNA修饰相关基因进行综合分析，以用于DCM的诊断和亚型分类。
我们从基因表达综合数据库（GEO）微阵列数据集中收集了DCM和对照样本的RNA修饰相关基因。使用R语言中的“Limma”包对这些基因进行差异表达分析。采用单变量逻辑回归和LASSO算法来确定用于建立诊断模型的最佳基因。此外，使用ConsensusClusterPlus来识别RNA修饰分子亚型。最后，利用临床样本和小鼠模型证实了关键RNA修饰相关基因的表达及其与DCM的关联。
26个RNA修饰相关基因在DCM中被鉴定为失调，这些基因之间存在紧密联系。基于13个基因（ 、 和 ）构建的诊断模型，其曲线下面积（AUC）为0.980，对DCM具有良好的预测能力。浸润的血浆B细胞、嗜酸性粒细胞、CD8 T细胞和调节性T细胞与 、 和 密切相关。鉴定出两种RNA修饰分子亚型（簇1和簇2）。簇1的RNA修饰评分更高，免疫评分更低，HLA - DRB1和HLA - DPB1表达低于簇2。簇2参与代谢相关途径，而簇1激活肾素 - 血管紧张素系统途径。我们还进一步发现，在13个关键RNA修饰相关基因中，心脏功能降低与 的上调以及 的下调之间存在显著关联。
总之，我们基于RNA修饰的诊断模型对DCM具有良好的预测能力。发现的两种RNA修饰分子亚组和四个关键枢纽基因可能有助于按风险对DCM患者进行分层。
