Unravelling the role of hub genes associated with cardio renal syndrome through an integrated bioinformatics approach

Interactions of the heart and kidney provide basis for the cardiorenal syndrome, a condition in which failure of one organ (either the heart or the kidney) leads to, or exacerbates, failure of the other organ. This heterogeneous and complex clinical entity is linked to higher morbidity and mortality, thus, warranting identification of novel molecular biomarkers that can be implemented to early diagnosis of cardiorenal syndrome (CRS) patients and to predict their disease stage and clinical outcome. Here, we used a microarray dataset for the identification of key differentially expressed genes (DEGs). Initial analysis based on the cut off criteria [i.e., p -value 0.5] revealed 11 upregulated and 10 down-regulated DEGs. All these 21 DEGs were subjected to network analysis separately that showed 5 genes (ADRB2, DAB2, CX3CR1, DHRS9 and CCZ1B) in upregulated and 6 genes (FOS, FOSB, EGR1, ABCA1, DUSP1, and CXCL8) in downregulated network modules. Ten functionally enriched DEGs out of 11 were further subjected to determine the cardiorenal syndrome-specific miRNA-mRNA regulatory network. Finally, resulting 12 node network revealed 4 hub genes (DAB2: upregulated and FOS, EGR1, and CXCL8: downregulated) associated with 8 miRNAs (hsa-let-7b-5p, hsa-miR-17-5p, hsa-miR-147a, hsa-miR-16-5p, hsa-miR-129-2-3p, hsa-miR-124,3p, hsa-miR-20a-5p, and hsa-miR-429). In Feed-Forward Loop (FFL) analysis among these four hub genes, three namely DAB2, FOS and EGR1 showed their roles in regulation and inhibition. With the assumption of this disease candidate gene prioritization, we report that DAB2, FOS, EGR1 and CXCL8 may serve as robust biomarkers in CRS.