Integrated Analysis of the Immune Infiltration Pattern and Novel Diagnostic Biomarkers in Septic Cardiomyopathy.

PURPOSE: In this study, various informatics analyses were employed to identify the hub genes associated with septic cardiomyopathy (SCM) onset and investigate their immune infiltration status.

METHODS

High-throughput sequencing data of myocardial tissue samples from mice with SCM were obtained from the GEO database and our previously published articles. The Limma and weighted gene co-expression network analysis (WGCNA) packages were used to identify the hub genes associated with SCM onset. GSEA and the DAVID database were employed for gene enrichment analysis. Additionally, the CIBERSORT database was used to analyze the immune infiltration in SCM. Finally, the multiMiR package was used to analyze the microRNAs acting as ceRNAs for the hub genes. Receiver operating characteristic (ROC) curves and Mendelian randomization analysis were used to evaluate the predictive value of hub genes for SCM.

RESULTS

The SCM group included nine samples, while the control group included ten samples. SCM upregulated 15 genes and downregulated 7. Mt1 and Actc1 were the most significantly upregulated and downregulated, respectively. GO analysis indicated that the most significantly enriched biological process was "response to bacterium," and the most enriched signaling pathway was "mineral absorption." Immunoinfiltration analysis revealed decreased T cells CD4 naive, B cells naive, resting mast cells, and M2 macrophage infiltration in the hearts of SCM mice. WGCNA and Limma package analyses identified Clu, Igf1, and Trp53 as hub genes associated with SCM onset. The ROC curves demonstrated a strong correlation and predictive value for Trp53, Igf1, and Clu in the SCM. Moreover, Clu and Igf1 demonstrated predictive values for SCM using Mendelian randomization analysis from the IEU database. Eleven miRNAs formed a ceRNA network with these hub genes.

CONCLUSION

In summary, our results implicated Igf1 and Clu as the potential candidates involved in SCM pathogenesis.