Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
BMC Med Genomics. 2022 Mar 27;15(1):72. doi: 10.1186/s12920-022-01221-z.
Heart failure (HF) is the most common potential cause of death, causing a huge health and economic burden all over the world. So far, some impressive progress has been made in the study of pathogenesis. However, the underlying molecular mechanisms leading to this disease remain to be fully elucidated.
The microarray data sets of GSE76701, GSE21610 and GSE8331 were retrieved from the gene expression comprehensive database (GEO). After merging all microarray data and adjusting batch effects, differentially expressed genes (DEG) were determined. Functional enrichment analysis was performed based on Gene Ontology (GO) resources, Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, gene set enrichment analysis (GSEA), response pathway database and Disease Ontology (DO). Protein protein interaction (PPI) network was constructed using string database. Combined with the above important bioinformatics information, the potential key genes were selected. The comparative toxicological genomics database (CTD) is used to explore the interaction between potential key genes and HF.
We identified 38 patients with heart failure and 16 normal controls. There were 315 DEGs among HF samples, including 278 up-regulated genes and 37 down-regulated genes. Pathway enrichment analysis showed that most DEGs were significantly enriched in BMP signal pathway, transmembrane receptor protein serine/threonine kinase signal pathway, extracellular matrix, basement membrane, glycosaminoglycan binding, sulfur compound binding and so on. Similarly, GSEA enrichment analysis showed that DEGs were mainly enriched in extracellular matrix and extracellular matrix related proteins. BBS9, CHRD, BMP4, MYH6, NPPA and CCL5 are central genes in PPI networks and modules.
The enrichment pathway of DEGs and GO may reveal the molecular mechanism of HF. Among them, target genes EIF1AY, RPS4Y1, USP9Y, KDM5D, DDX3Y, NPPA, HBB, TSIX, LOC28556 and XIST are expected to become new targets for heart failure. Our findings provide potential biomarkers or therapeutic targets for the further study of heart failure and contribute to the development of advanced prediction, diagnosis and treatment strategies.
心力衰竭（HF）是全球最常见的潜在死亡原因，给全球带来了巨大的健康和经济负担。迄今为止，在发病机制的研究方面已经取得了一些令人瞩目的进展。然而，导致这种疾病的潜在分子机制仍有待充分阐明。
从基因表达综合数据库（GEO）中检索 GSE76701、GSE21610 和 GSE8331 的微阵列数据集。合并所有微阵列数据并调整批次效应后，确定差异表达基因（DEG）。基于基因本体论（GO）资源、京都基因与基因组百科全书（KEGG）资源、基因集富集分析（GSEA）、应答途径数据库和疾病本体论（DO）进行功能富集分析。使用字符串数据库构建蛋白质-蛋白质相互作用（PPI）网络。结合上述重要的生物信息学信息，选择潜在的关键基因。使用比较毒理学基因组学数据库（CTD）探索潜在关键基因与 HF 之间的相互作用。
我们鉴定了 38 例心力衰竭患者和 16 例正常对照。HF 样本中有 315 个 DEG，包括 278 个上调基因和 37 个下调基因。通路富集分析表明，大多数 DEG 显著富集于 BMP 信号通路、跨膜受体蛋白丝氨酸/苏氨酸激酶信号通路、细胞外基质、基底膜、糖胺聚糖结合、硫化合物结合等。同样，GSEA 富集分析表明，DEG 主要富集于细胞外基质和细胞外基质相关蛋白。BBS9、CHRD、BMP4、MYH6、NPPA 和 CCL5 是 PPI 网络和模块中的核心基因。
DEG 和 GO 的富集通路可能揭示了 HF 的分子机制。其中，EIF1AY、RPS4Y1、USP9Y、KDM5D、DDX3Y、NPPA、HBB、TSIX、LOC28556 和 XIST 等靶基因有望成为心力衰竭的新靶点。我们的研究结果为心力衰竭的进一步研究提供了潜在的生物标志物或治疗靶点，并有助于开发先进的预测、诊断和治疗策略。
