Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods

Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language. Pathway enrichment analysis of DEGs was then performed. Meanwhile, the potential transcription factors (TFs) and microRNAs (miRNAs) of these DEGs were predicted based on their binding sequences. In addition, DEGs were mapped to the cMap database to find the potential small molecule drugs. A total of 4777 genes were identified as DEGs by comparing gene expression profiles between DCM and control samples. DEGs were significantly enriched in 26 pathways, such as lymphocyte TarBase pathway and androgen receptor signaling pathway. Furthermore, potential TFs (SP1, LEF1, and NFAT) were identified, as well as potential miRNAs (miR-9, miR-200 family, and miR-30 family). Additionally, small molecules like isoflupredone and trihexyphenidyl were found to be potential therapeutic drugs for DCM. The identified DEGs (PRSS12 and FOXG1), potential TFs, as well as potential miRNAs, might be involved in DCM.

扩张型心肌病（Dilated cardiomyopathy, DCM）以心室扩张为核心特征，是引发心力衰竭与心脏移植的常见病因。本研究拟通过生物信息学手段，探究潜在的DCM相关基因及其潜在调控机制。研究从基因表达综合数据库（Gene Expression Omnibus, GEO）下载了GSE3586的基因表达谱数据，该数据集包含15例正常对照样本与13例DCM患者样本。采用R语言的Limma包，识别正常样本与DCM样本间的差异表达基因（differentially expressed genes, DEGs）。随后对筛选得到的DEGs开展通路富集分析。同时，基于结合序列预测这些DEGs的潜在转录因子（transcription factors, TFs）与微小RNA（microRNAs, miRNAs）。此外，将DEGs映射至cMap数据库，以筛选潜在的小分子治疗药物。通过对比DCM样本与对照样本的基因表达谱，本研究共鉴定出4777个DEGs。DEGs显著富集于26条通路，包括淋巴细胞TarBase通路、雄激素受体信号通路等。进一步研究鉴定出SP1、LEF1及NFAT等潜在转录因子，以及miR-9、miR-200家族与miR-30家族等潜在miRNAs。此外，本研究发现异氟泼尼龙（isoflupredone）与三己芬迪（trihexyphenidyl）等小分子可作为DCM的潜在治疗药物。本研究鉴定的DEGs PRSS12与FOXG1、潜在转录因子及潜在miRNAs，可能参与DCM的发生与发展过程。