Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China.
Front Biosci (Landmark Ed). 2022 Aug 17;27(8):246. doi: 10.31083/j.fbl2708246.
Dilated cardiomyopathy (DCM) is one of the main causes of systolic heart failure and frequently has a genetic component. The molecular mechanisms underlying the onset and progression of DCM remain unclear. This study aimed to identify novel diagnostic biomarkers to aid in the treatment and diagnosis of DCM.
The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, GSE120895 and GSE17800, which were subsequently merged into a single cohort. Differentially expressed genes were analyzed in the DCM and control groups, followed by weighted gene coexpression network analysis to determine the core modules. Core nodes were identified by gene significance (GS) and module membership (MM) values, and four hub genes were predicted by the Lasso regression model. The expression levels and diagnostic values of the four hub genes were further validated in the datasets GSE19303. Finally, potential therapeutic drugs and upstream molecules regulating genes were identified.
The turquoise module is the core module of DCM. Four hub genes were identified: GYPC (glycophorin C), MLF2 (myeloid leukemia factor 2), COPS7A (COP9 signalosome subunit 7A) and ARL2 (ADP ribosylation factor like GTPase 2). Subsequently, Hub genes showed significant differences in expression in both the dataset and the validation model by real-time quantitative PCR (qPCR). Four potential modulators and seven chemicals were also identified. Finally, molecular docking simulations of the gene-encoded proteins with small-molecule drugs were successfully performed.
The results suggested that ARL2, MLF2, GYPC and COPS7A could be potential gene biomarkers for DCM.
扩张型心肌病（DCM）是收缩性心力衰竭的主要原因之一，且常具有遗传成分。DCM 发病和进展的分子机制尚不清楚。本研究旨在寻找新的诊断生物标志物，以辅助 DCM 的治疗和诊断。
从基因表达综合数据库（GEO）中提取两个微阵列数据集 GSE120895 和 GSE17800，然后将其合并为一个单一队列。在 DCM 和对照组中分析差异表达基因，接着进行加权基因共表达网络分析以确定核心模块。通过基因显著性（GS）和模块成员性（MM）值确定核心节点，并通过 Lasso 回归模型预测 4 个枢纽基因。进一步在数据集 GSE19303 中验证 4 个枢纽基因的表达水平和诊断价值。最后，鉴定潜在的治疗药物和调控基因的上游分子。
turquoise 模块是 DCM 的核心模块。鉴定出 4 个枢纽基因：GYPC（糖蛋白 C）、MLF2（髓样白血病因子 2）、COPS7A（COP9 信号osome 亚基 7A）和 ARL2（ADP 核糖基化因子样 GTPase 2）。随后，实时定量 PCR（qPCR）显示这 4 个枢纽基因在数据集和验证模型中的表达均存在显著差异。还鉴定出 4 个潜在调节剂和 7 种化学物质。最后，成功进行了基因编码蛋白与小分子药物的分子对接模拟。
结果表明，ARL2、MLF2、GYPC 和 COPS7A 可能是 DCM 的潜在基因生物标志物。
