Identification of Candidate Biomarkers for Salt Sensitivity of Blood Pressure by Integrated Bioinformatics Analysis.

ABSTRACT

In the current study, we aimed to identify potential biomarkers for salt sensitivity of blood pressure (SSBP), which may provide a novel insight into the pathogenic mechanisms of salt-sensitive hypertension. Firstly, we conducted weighted gene coexpression network analysis (WGCNA) and selected a gene module and 60 hub genes significantly correlated to SSBP. Then, GO function and KEGG signaling pathway enrichment analysis and protein-protein interaction (PPI) network analysis were performed. Furthermore, we identified a five-gene signature with high connectivity degree in the PPI network and high AUC of ROC curves, which may have high diagnosis value for SSBP. Moreover, through combining two gene screening methods, we identified 23 differentially expressed circRNAs and selected the top 5% circRNAs (1 circRNA) with the highest connectivity degree in the coexpression network as hub circRNA highly associated with SSBP. Finally, we carried out RT-qPCR to validate the expression of five hub genes, and our results showed that the expression of HECTD1 (P = 0.017), SRSF5 (P = 0.003), SRSF1 (P = 0.006), HERC2 (P = 0.004), and TNPO1 (P = 0.002) was significantly upregulated in the renal tissue in salt-sensitive rats compared to salt-resistant rats, indicating that these five hub genes can serve as potential biomarkers for SSBP.