STAT3-CD163 cross-talk exhibits promising biomarkers for a progressive ischemic cardiomyopathy: integrative computational and gene expression profiling based on Gene Expression Omnibus datasets

Abstract

Background and purpose: Ischemic heart disease frequently leads to heart failure, often resulting in death. In this study, we aimed to identify common hub mRNAs and pathways involved in the pathological progression of ischemic cardiomyopathy (ICM). Methods: Validation quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out on peripheral blood and left ventricle specimens from patients in three groups with stable coronary artery disease (CAD), myocardial infarction (MI), and ICM and compared with corresponding controls. qRT-PCR was preceded by computational analysis of eight high-throughput RNA sequencing and microarray datasets from 499 patients and 233 controls, to determine possible common biologically meaningful differentially expressed genes (DEGs). To determine the potential pathological pathways, we performed Gene Ontology functional annotation, pathway enrichment analysis, protein–protein interaction (PPI) analysis, and constructed transcriptional factor/miRNA regulatory networks. Finally, approved drugs were screened. Results: Fifteen common DEGs with P < 0.01 were identified. STAT3, CEBPD, GLUL, and CD163 were hub-enriched mRNAs with an interaction score ≥ 0.50. Our qRT-PCR analysis showed an increased expression of STAT3 in all three patient groups and CD163, mainly in cardiac samples, in a remarkably ascending manner. Interaction modules showed co-regulators supporting high STAT3-CD163 connectivity, suggesting a potential role for STAT3-CD163 cross-talk-mediated inflammatory responses in ICM progression. Conclusions: Our results provided a novel perspective for understanding the underlying mechanisms of ICM progression and exploring new therapeutic agents. Clinical trial registration: URL: www.clinicaltrials.gov. Unique identifier: NCT05508269.