Identificação de microRNA diferencialmente expressos em pacientes com disfunção cardíaca decorrente de sepse e a correlação com as vias intracelulares de sinalização: análise in silico de potenciais biomarcadores de diagnóstico

Abstract

Introduction: Sepsis is a clinical condition with a high risk of death, defined as an organ dysfunction resulting from a dysregulated host response to infection, with cardiac dysfunction being one of the main complications in septic patients and closely associated with high mortality induced by this clinical condition. Currently, the incidence and mortality of sepsis remain high, highlighting the importance of using biomarkers for early diagnosis and prognosis. In this scenario, microRNAs emerge as potential candidates with high specificity and sensitivity for sepsis. In light of this context, the present study aimed to investigate the expression profile of miRNAs and their correlation with intracellular pathways involved in myocardial remodeling associated with sepsis. Methods & Results: Surveying publicly available transcriptomes in NCBI, GEO dataset, and ENA resulted in obtaining the dataset GSE171546. This dataset comprises 20 samples: 5 in the control group and 15 samples in the septic cardiomyopathy group, divided into three time intervals: 24h, 48h, and 72h. Importation and analysis of this dataset were performed using the online Galaxy platform. The p-value <0.05 and fold change were evaluated to identify Differentially Expressed Genes (DEGs) and Differentially Expressed microRNAs (DEMs). From this analysis, 768 DEGs were found at the 24h time point, 312 in the 48h group, and 255 DEGs in the 72h interval, along with two DEMs (miR-8110 and miR-574-5p). Pathway enrichment analysis and gene ontology were performed using Webgestalt. The validation of target mRNAs of DEMs was carried out through Mirwalk, followed by the construction of an interaction network between DEGs and DEMs using Cytoscape. Conclusion: The two identified microRNAs are related to various intracellular pathways involved in myocardial remodeling associated with cardiac dysfunction resulting from sepsis and are differentially modulated in the transcriptome analyzed in this study, suggesting a relevant role as potential prognostic biomarkers for sepsis-induced cardiomyopathy.