RPS27A as a potential clock-related diagnostic biomarker for myocardial infarction: Comprehensive bioinformatics analysis and experimental validation

Abstract

Background  The circadian system plays a crucial role in managing cardiovascular functions, with disturbances in this system associated with Myocardial Infarction (MI). Despite this connection, the exact mechanisms by which clock genes influence MI occurrence are not well-defined. This research focused on investigating the link between clock genes and MI.

Methods  The authors examined MI microarray datasets (GSE151412 and GSE60993) from the GEO database, concentrating on Differentially Expressed Genes (DEGs) associated with the circadian system. To clarify critical biological functions and pathways, the authors performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Through Lasso regression, the authors pinpointed hub genes and confirmed their relevance using both the GSE66360 dataset and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Furthermore, the authors conducted single-Gene Set Enrichment Analysis (GSEA) to reveal pathways linked to the hub gene. The analysis extended to exploring drug interactions and networks involving competing endogenous RNA (ceRNA).

Results  The present analysis identified ten clock genes associated with circadian rhythms that showed differential expression between MI patients and healthy controls. Enrichment analysis suggested these genes’ roles in pathways like the Gap junction and circadian rhythm pathways. Following Lasso regression and validation, RPS27A was identified as the main hub gene. GSEA further highlighted enriched pathways, such as mismatch repair. Additionally, immune infiltration analysis revealed notable differences in B-cell and CD4+ T-cell populations between the MI group and the control group.

Conclusion  The present findings suggest that the clock-related gene RPS27A is associated with MI, potentially influencing its development through circadian rhythm regulation. These results enhance the understanding of MI pathogenesis and may offer new avenues for therapeutic intervention.