TITLE:
Identification and Validation of Novel Biomarkers Related to the Calcium Metabolism Pathway in Hypertension Patients Based on Comprehensive Bioinformatics Methods
AUTHORS:
Xiangguang Chang, Lei Guo, Liying Zou, Yazhao Ma, Jilin Feng
KEYWORDS:
Hypertension, Biomarkers, Differentially Expressed Genes, Ca2+ Metabo-lism, Bioinformatics Analysis
JOURNAL NAME:
Health,
Vol.16 No.3,
March
18,
2024
ABSTRACT: Background: Hypertension is a universal
risk factor for cardiovascular diseases and is thus the leading cause of death
worldwide. The identification of novel
prognostic and pathogenesis biomarkers plays a key role in disease management. Methods: The GSE145854 and
GSE164494 datasets were downloaded
from the Gene Expression Omnibus (GEO) database and used for screening and validating hypertension signature
genes, respectively. Gene Ontology (GO) enrichment analysis was
performed on the differentially expressed genes (DEGs) related to calcium ion
metabolism in patients with hypertension. The core genes related to immune
infiltration were analyzed and screened, and the activity of the signature
genes and related pathways was quantified using gene set enrichment analysis
(GSEA). The infiltration of immune cells in the blood samples was analyzed, and
the DEGs that were abnormally expressed in the clinical blood samples of
patients with hypertension were verified via RT-qPCR. Results: A total of 176 DEGs were screened. GO showed
that DEGs was involved in the regulation of calcium ion metabolism in biological processes (BP), actin mediated
cell contraction, negative regulation of cell movement, and calcium ion
transmembrane transport, and in the
regulation of protease activity in molecular functions (MF). KEGG analysis revealed that the DEGs were involved mainly in
the cGMP-PKG signaling pathway, ubiquitin-protein transferase, tight junction-associated proteins, and the
regulation of myocardial cells. MF analysis revealed the immune infiltration function of the cells. RT-qPCR revealed that the expression of Cacna1d,
Serpine1, Slc8a3, and Trpc4 was up regulated
in hypertension, the
expression of Myoz2 and Slc25a23 was down regulated. Conclusion: Cacna1d, Serpine1, Slc8a3, Trpc4, Myoz2 and Slc25a23 may be
involved in the regulation of calcium
metabolism pathways and play key roles in hypertension. These
differentially expressed calcium metabolism-related genes may serve as
prognostic markers of hypertension.