Unveiling the Molecular Landscape of Heart Failure: A Bioinformatics Approach Identifies Novel Diagnostic Biomarkers and Therapeutic Targets

Heart failure is a critical endpoint of cardiovascular diseases, with a complex molecular mechanism that remains largely obscure. In this study, we aimed to systematically investigate the underlying molecular mechanisms, as well as the diagnostic and therapeutic targets of heart failure using bioinformatics. To achieve this, we obtained 8 healthy samples and 8 heart failure samples from GSE8331 and GSE76701. After removing the batch effect, we performed differential analysis and obtained 185 differentially expressed IDs. Our enrichment analysis revealed that the molecular mechanisms of heart failure were primarily related to immune, inflammation, and metabolism-related pathways. Furthermore, we conducted an immune cell infiltration analysis, which showed that Tgd cells and Neurons were significantly enriched in heart failure samples, while pDCs and NKTs were more abundant in healthy tissue samples.

Through PPI network analysis, we identified hub genes that included EGR1, EGR2, FOS, and FOSB. We then established a 4-gene diagnostic model using these hub genes and validated it in GSE21610 and GSE57338. Additionally, we evaluated the discriminative ability of the hub genes using the ROC curve. The 4-gene diagnostic model demonstrated an AUC value of 0.775 and 0.877 in GSE21610 and GSE57338, respectively.

In conclusion, our study explored the underlying molecular mechanisms of heart failure and the immune cell infiltration environment of failing myocardium through bioinformatic analysis of the GEO dataset. We also identified EGR1, EGR2, FOS, and FOSB as potential diagnostic biomarkers and therapeutic targets for heart failure. Most significantly, our 4-gene diagnostic model offers a new understanding of the pathogenesis of heart failure and may serve as an exciting target for future in-depth research.