Differences in T cell-associated serum markers between ischemic cardiomyopathy and dilated cardiomyopathy

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Abstract
Background: Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) have similar clinical manifestations but differ in pathogenesis. We aimed to identify T cell-associated serum markers that can be used to distinguish between ICM and DCM. Methods: We identified differentially expressed genes (DEGs) with transcriptome sequencing data in GSE116250, and then conducted enrichment analysis of DEGs in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interaction (PPI) networks were used to analyze the relationship between T cells-related genes and identify hub genes. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect T cell-associated proteins in serum, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of these serum markers. Results: Using the limma package and Venn plots, we found that the non-failing donors (NFD) and DCM groups shared many of the same DEGs and DEGs-enriched functions compared to the ICM group, which were involved in T cell activation and differentiation, among other functions. Subsequently, the immune cell score showed no difference between NFD and DCM, but they were significantly different from ICM patients in CD8 T cells CD4 T cells memory resting and activated, T cells follicular helper, and M1 macrophage. After analyzing T cell-associated DEGs, it was found that 4 DEGs encoding secreted proteins were highly expressed in the ICM group compared with the NFD and DCM groups, namely chemokine (C-C motif) ligand 21 (CCL21), interleukin (IL)-1β, lymphocyte-activation gene 3 (LAG3), and vascular cell adhesion molecule-1 (VCAM-1). Importantly, the serum levels of CCL21, IL-1β, LAG3, and VCAM-1 in ICM patients were all significantly higher than those in DCM patients. The ROC curves showed that the area under the curve (AUC) values of serum CCL21, IL-1β, LAG3, and VCAM-1 were 0.775, 0.868, 0.934, and 0.903, respectively. Conclusions: We have identified four T cell-associated serum markers, CCL21, IL-1β, LAG3, and VCAM-1, as potential diagnostic serum markers that differentiate ICM from DCM.

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