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

TL;DR

This study identifies key genes and immune patterns in septic cardiomyopathy using data analysis and highlights potential biomarkers for diagnosis.

Contribution

The study introduces novel diagnostic biomarkers (Igf1 and Clu) and reveals immune infiltration patterns specific to septic cardiomyopathy.

Findings

SCM upregulated Mt1 and downregulated Actc1, with Clu, Igf1, and Trp53 identified as hub genes.

Immune infiltration analysis showed reduced T cells, B cells, mast cells, and M2 macrophages in SCM hearts.

Clu and Igf1 showed strong predictive value for SCM using ROC and Mendelian randomization analyses.

Abstract

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.

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.

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.

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

In this study, various informatics analyses were employed to identify hub genes associated with the onset of septic cardiomyopathy and investigate its immune infiltration status.

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