Exploration and validation of signature genes and immune associations in septic cardiomyopathy

ABSTRACT

An early and accurate diagnosis of septic cardiomyopathy is vital for improving the overall prognosis of sepsis. In our research, we aimed to identify signature genes and their immune connections in septic cardiomyopathy. By analyzing the mouse myocardial transcriptome from sepsis induced by cecum ligation and puncture (CLP), we identified four distinct k-means clusters. Further analysis of human myocardial datasets using Weighted Gene Co-expression Network Analysis (WGCNA) revealed a strong correlation between the MEturquoise module and septic cardiomyopathy (cor = 0.79, p < .001). Through the application of Cytoscape plug-in MCODE and comprehensive analysis, we pinpointed two signature genes, THBS1 and TIMP1. These genes demonstrated significant involvement in immune cell infiltration, as detected by CIBERSORT, and displayed promising prognostic potential as validated by external datasets. Our experimental validation confirmed the up-regulation of both THBS1 and TIMP1 in septic murine hearts, underscoring their positive association with septic cardiomyopathy.

KEYWORDS:

• Septic cardiomyopathy
• weighted gene co-expression network analysis
• immune infiltration analysis

Acknowledgments

Zhengbo Zhao, Songbai Deng, Jianlin Du designed the study and drafted the manuscript. Zhengbo Zhao, Xiaojing wang, Fangyan Tan analyzed data and typeset figures. Performed the experimental procedures: Fangyan Tan, Zhengbo Zhao, Xiaojing. Zhengbo Zhao, Xiaojing, Han Liu, Wan Chen, Jing Wang conducted the bioinformatics and statistical analyses. Zhengbo Zhao, Xiaojing wang, Songbai Deng, Jianlin Du revised the manuscript. All authors contributed to the article and approved the submitted version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/10641963.2024.2302570

Additional information

Funding

This work was supported by the Natural Science Foundation of Chongqing Science and Technology Commission under Grant [cstc2020jcyj-msxmX0919],CQMU Program for Youth Innovation in Future Medicine [W0133], the Senior Medical Talents Program of Chongqing for Young and Middle-Aged, and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University.