STAT3-CD163 crosstalk exhibits promising biomarkers for a progressive Ischemic cardiomyopathy; integrative computational and gene expression profiling based on GEO datasets

Abstract

Background:Ischemic heart diseaseis one of the heaviest health-related burdens worldwide.We aimed to identify the common hub mRNA and pathways that are involved in pathological progression of ischemic cardiomyopathy(ICM). Methods:To explore potential differentially expressed genes (DEGs) of all ischemic heart disease stages, we used chipster and GEO2R tools to analyze of retrieved eight high throughput RNA datasets obtained from GEO database. Gene Ontology functional annotation and Pathways enrichment analyses were used to obtain the common functional enriched DEGs which were visualized in protein–protein interactions (PPI) network to explore the hub mRNA according to the interaction scores. Validation qRT-PCR was carried out for blood and cardiac biopsies compared with controls to validate the determined four hub mRNAs and subsequently reviewed inside comprehensive published meta-analysis database. The validated mRNAs were visualized in two interaction modules. Finally screening of approved drugs was applied. Results: 15 common DEGs with p value ≤ 0.01 were identified and carbohydrate &amino acids metabolism and inflammatory responses were significantly enriched. STAT3, CEBPD, GLUL and CD163 were hub enriched mRNAs with interaction score ≥ 0.50. Our qRT-PCR analysis showed increased expression of STAT3 over all patients groups and CD163 mainly in cardiac samples with remarked ascending manner. Interaction modules showed co-regulators supporting high STAT3-CD163 connectivity providing potential role of STAT3-CD163 crosstalk mediated inflammatory responses in ICM progression. We determined two reported drugs targeting STAT3. Conclusion:Post analysis of the used GEO datasets and qRT-PCR data pointed that STAT3-CD163 crosstalk was potential biomarkers for ICM progression. Clinical trial registration: www.clinicaltrials.gov, Identifier: NCT05508269