Uncovering Shared Transcriptomic Changes between Cardiogenic and Septic Shock and Identification of Gene Signature Specific to Septic Shock

Abstract

Background: Shock is a complex physiological syndrome. Although the two most common types—septic shock and cardiogenic shock—have similar presentations, their etiologies differ. Therefore, this study was conducted to investigate the transcriptomic responses to septic shock and cardiogenic shock and the related molecular mechanisms. Methods: The GSE131411 (GEO Series) and GSE57065 microarray datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes were identified by analysis of variance, and expression patterns at three time points were analyzed using Short Time-series Expression Miner. Functional enrichment analysis was conducted using the clusterProfiler package in R, and microRNA (miRNA)-messenger RNA (mRNA) interactions were predicted with the miRWalk v3.0 platform. Characteristic genes associated with septic shock were identified and confirmed using a support vector machine model. Results: In total, 28 genes were found to be differentially expressed in response to both septic shock and cardiogenic shock. These common differentially expressed genes were mainly enriched in the systemic lupus erythematosus pathway as well as in several biological processes (including the humoral immune response and phagocytosis). Furthermore, 467 interactions comprising 191 miRNAs and 150 mRNAs were established in the miRNA-mRNA network. The differentially expressed genes unique to the septic shock response were mainly enriched in the cytokine-cytokine receptor interaction and proteoglycans in cancer pathways as well as in the T-cell activation and leukocyte migration processes. AURKB (aurora kinase B), CEACAM6 (CEA cell adhesion molecule 6), AZU1 (azurocidin 1), DEFA4 (defensin alpha 4), CHI3L1 (chitinase 3 like 1), and FCER1A (Fc epsilon receptor 1a) were identified as characteristic septic shock-related genes, and the support vector machine model based on these six genes showed better predictive performance than that of previously identified genes associated with sepsis. Conclusions: The development of cardiogenic shock and septic shock involved changes in gene expression patterns. Several characteristic genes that distinguish septic shock were identified. This study provides a basis for distinguishing between cardiogenic shock and septic shock and is expected to improve diagnosis and guide treatment choices.