Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Genes (Basel). 2022 Mar 17;13(3):530. doi: 10.3390/genes13030530.
Hypertrophic cardiomyopathy (HCM) is a genetic heterogeneous disorder and the main cause of sudden cardiac death in adolescents and young adults. This study was aimed at identifying potential diagnostic biomarkers and biological pathways to help to diagnose and treat HCM through bioinformatics analysis. We selected the GSE36961 dataset from the Gene Expression Omnibus (GEO) database and identified 893 differentially expressed genes (DEGs). Subsequently, 12 modules were generated through weighted gene coexpression network analysis (WGCNA), and the turquoise module showed the highest negative correlation with HCM (cor = −0.9, p-value = 4 × 10−52). With the filtering standard gene significance (GS) < −0.7 and module membership (MM) > 0.9, 19 genes were then selected to establish the least absolute shrinkage and selection operator (LASSO) model, and LYVE1, MAFB, and MT1M were finally identified as key genes. The expression levels of these genes were additionally verified in the GSE130036 dataset. Gene Set Enrichment Analysis (GSEA) showed oxidative phosphorylation, tumor necrosis factor alpha-nuclear factor-κB (TNFα-NFκB), interferon-gamma (IFNγ) response, and inflammatory response were four pathways possibly related to HCM. In conclusion, LYVE1, MAFB, and MT1M were potential biomarkers of HCM, and oxidative stress, immune response as well as inflammatory response were likely to be associated with the pathogenesis of HCM.
肥厚型心肌病（HCM）是一种遗传异质性疾病，也是青少年和年轻成年人心源性猝死的主要原因。本研究旨在通过生物信息学分析，确定潜在的诊断生物标志物和生物学途径，以帮助诊断和治疗 HCM。我们从基因表达综合数据库（GEO）中选择了 GSE36961 数据集，并鉴定了 893 个差异表达基因（DEGs）。随后，通过加权基因共表达网络分析（WGCNA）生成了 12 个模块，其中绿松石模块与 HCM 的相关性最高（cor=-0.9，p 值=4×10−52）。根据基因显著性（GS）<−0.7 和模块成员性（MM）>0.9 的过滤标准，筛选出 19 个基因，建立最小绝对收缩和选择算子（LASSO）模型，最终确定 LYVE1、MAFB 和 MT1M 为关键基因。这些基因的表达水平在 GSE130036 数据集上进一步验证。基因集富集分析（GSEA）显示，氧化磷酸化、肿瘤坏死因子α-核因子κB（TNFα-NFκB）、干扰素-γ（IFNγ）反应和炎症反应可能与 HCM 相关。总之，LYVE1、MAFB 和 MT1M 可能是 HCM 的潜在生物标志物，氧化应激、免疫反应和炎症反应可能与 HCM 的发病机制有关。
