Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int J Med Sci. 2024 Jul 8;21(9):1769-1782. doi: 10.7150/ijms.92537. eCollection 2024.
Dilated cardiomyopathy (DCM) causes heart failure and sudden death. Epigenetics is crucial in cardiomyopathy susceptibility and progression; however, the relationship between epigenetics, particularly DNA methylation, and DCM remains unknown. Therefore, this study identified aberrantly methylated differentially expressed genes (DEGs) associated with DCM using bioinformatics analysis and characterized their clinical utility in DCM. DNA methylation expression profiles and transcriptome data from public datasets of human DCM and healthy control cardiac tissues were obtained from the Gene Expression Omnibus public datasets. Then an epigenome-wide association study was performed. DEGs were identified in both DCM and healthy control cardiac tissues. In total, 3,353 cytosine-guanine dinucleotide sites annotated to 2,818 mRNAs were identified, and 479 DCM-related genes were identified. Subsequently, core genes were screened using logistic, least absolute shrinkage and selection operator, random forest, and support vector machine analyses. The overlapping of these genes resulted in DEGs with abnormal methylation patterns. Cross-tabulation analysis identified 8 DEGs with abnormal methylation. Real-time quantitative polymerase chain reaction confirmed the expression of aberrantly methylated DEGs in mice. In DCM murine cardiac tissues, the expressions of were higher compared to normal murine cardiac tissues. Moreover, logistic regression model associated with aberrantly methylated DEGs was developed to evaluate the diagnostic value, and the area under the receiver operating characteristic curve was 0.949, indicating that the diagnostic model could reliably distinguish DCM from non-DCM samples. In summary, our study identified 5 DEGs through integrated bioinformatic analysis and experiments, which could serve as potential targets for further comprehensive investigation.
扩张型心肌病（DCM）可导致心力衰竭和猝死。表观遗传学在心肌病易感性和进展中起着至关重要的作用；然而，表观遗传学，特别是 DNA 甲基化与 DCM 之间的关系尚不清楚。因此，本研究通过生物信息学分析，确定了与 DCM 相关的异常甲基化差异表达基因（DEG），并对其在 DCM 中的临床应用进行了描述。从基因表达综合数据库公共数据集获取了人类 DCM 和健康对照心脏组织的 DNA 甲基化表达谱和转录组数据，然后进行了全基因组关联研究。在 DCM 和健康对照心脏组织中均鉴定到 DEG。总共鉴定到 3353 个注释到 2818 个 mRNAs 的胞嘧啶-鸟嘌呤二核苷酸位点，鉴定到 479 个与 DCM 相关的基因。随后，使用逻辑回归、最小绝对收缩和选择算子、随机森林和支持向量机分析筛选核心基因。这些基因的重叠导致了具有异常甲基化模式的 DEG。交叉制表分析鉴定到 8 个具有异常甲基化的 DEG。实时定量聚合酶链反应验证了异常甲基化 DEG 在小鼠中的表达。在 DCM 小鼠心脏组织中，与正常小鼠心脏组织相比，表达更高。此外，建立了与异常甲基化 DEG 相关的逻辑回归模型，以评估诊断价值，接受者操作特征曲线下的面积为 0.949，表明诊断模型可以可靠地区分 DCM 与非 DCM 样本。总之，通过综合生物信息学分析和实验，本研究鉴定到 5 个 DEG，它们可能成为进一步全面研究的潜在靶点。
