Left-sided heart failure (HF) is documented as a key prognostic factor in HF. However, the relative molecular mechanisms underlying left-sided HF is unknown. The purpose of this study is to unearth significant modules, pivotal genes and candidate regulatory components governing the progression of left-sided HF by bioinformatical analysis. A total of 319 samples in GSE57345 dataset were used for weighted gene correlation network analysis (WGCNA). ClusterProfiler package in R was used to conduct functional enrichment for genes uncovered from the modules of interest. Regulatory networks of genes were built using Cytoscape while Enrichr database was used for identification of transcription factors (TFs). The MCODE plugin was used for identifying hub genes in the modules of interest and their validation was performed based on GSE1869 dataset. A total of six significant modules were identified. Notably, the blue module was confirmed as the most crucially associated with left-sided HF, ischemic heart disease (ISCH) and dilated cardiomyopathy (CMP). Functional enrichment conveyed that genes belonging to this module were mainly those driving the extracellular matrix-associated processes such as extracellular matrix structural constituent and collagen binding. A total of seven transcriptional factors, including Suppressor of Zeste 12 Protein Homolog (SUZ12) and nuclear factor erythroid 2 like 2 (NFE2L2), adrenergic receptor (AR), were identified as possible regulators of coexpression genes identified in the blue module. A total of three key genes (OGN, HTRA1 and MXRA5) were retained after validation of their prognostic value in left-sided HF. The results of functional enrichment confirmed that these key genes were primarily involved in response to transforming growth factor beta and extracellular matrix. We uncovered a candidate gene signature correlated with HF, ISCH and CMP in the left ventricle, which may help provide better prognosis and therapeutic decisions and in HF, ISCH and CMP patients.

中文翻译：

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加权相关网络生物信息学揭示了驱动左侧心力衰竭的关键分子生物特征。

左侧心力衰竭（HF）被记录为HF的关键预后因素。但是，尚不清楚左侧HF的相对分子机制。这项研究的目的是通过生物信息学分析发现控制左侧HF进展的重要模块，关键基因和候选调控成分。GSE57345数据集中共有319个样本用于加权基因相关网络分析（WGCNA）。R中的ClusterProfiler软件包用于对从目标模块中发现的基因进行功能增强。基因的调控网络是使用Cytoscape建立的，而Enrichr数据库则用于鉴定转录因子（TF）。MCODE插件用于识别目标模块中的中枢基因，并根据GSE1869数据集进行了验证。总共确定了六个重要模块。值得注意的是，蓝色模块被确认与左侧HF，缺血性心脏病（ISCH）和扩张型心肌病（CMP）最相关。功能丰富表明，属于该模块的基因主要是那些驱动细胞外基质相关过程的基因，例如细胞外基质结构组成和胶原蛋白结合。总共七个转录因子，包括Zeste 12蛋白同源物的抑制子（SUZ12）和核因子类红细胞2样2（NFE2L2），肾上腺素能受体（AR），被确定为在蓝色模块中鉴定的共表达基因的可能调控因子。验证了它们在左侧HF中的预后价值后，总共保留了三个关键基因（OGN，HTRA1和MXRA5）。功能富集的结果证实，这些关键基因主要参与对转化生长因子β和细胞外基质的反应。我们在左心室中发现了与HF，ISCH和CMP相关的候选基因标记，这可能有助于为HF，ISCH和CMP患者提供更好的预后和治疗决策。