TY  - EJOU
AU  - Wang, Ying 
AU  - Zhang, Weijun 
AU  - Cai, Fei 
AU  - Tao, Yong 

TI  - Integrated Bioinformatics Analysis Identifies Vascular Endothelial Cell-Related Biomarkers for Hypertrophic Cardiomyopathy
T2  - Structural and Congenital Heart Disease

PY  - 2024
VL  - 19
IS  - 6
SN  - 3071-1738

AB  -  <b>Background:</b> Previous studies combined integrated scRNA-seq with bulk RNA data to screen biomarkers for cardiomyopathy. This study extended this approach to identify biomarkers specific for hypertrophic cardiomyopathy (HCM). <b>Methods:</b> Datasets GSE36961, GSE130036, GSE249925 and GSE203274 were analyzed in this study. ScRNA-seq analysis was employed to identify distinct cell populations. Differentially expression analysis was conducted to screen vascular endothelial cells (VECs)-related feature genes. After calculating VECs score, WGCNA was used to correlate gene modules with the VECs score. Key HCM biomarkers were determined using random forest analysis, and LASSO regression analyses to construct a diagnostic model based on their diagnostic efficacy and differential expression. <b>Results:</b> Our analysis identified nine distinct cell populations, with VECs accounting for a notably higher proportion in HCM samples. Genes associated with the VECs were enriched in the pathways related to blood vessel, immunity and cardiac function. After classifying significant gene modules based on VEC-related genes, a strong correlation between the blue module and the VECs score was detected. Notably, genes in the blue module were enriched in the pathways related to metabolism and immune response. Key genes with a high expression in HCM were determined by intersecting differentially expressed genes (DEGs) in HCM with those in the blue module. Finally, random forest analysis and LASSO regression analysis identified five central hub genes for the diagnosis of HCM, including Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1B (<i>DYRK1B</i>), Growth Arrest and DNA Damage Inducible Alpha (<i>GADD45A</i>), Influenza Virus NS1A Binding Protein (<i>IVNS1ABP</i>), Leiomodin 2 (<i>LMOD2</i>), and Pleckstrin Homology Like Domain Family B Member 2 (<i>PHLDB2</i>). <b>Conclusion:</b> Collectively, our study discovered novel VEC-related biomarkers for HCM and comprehensively examined the mechanisms underlying the pathogenesis of HCM.
KW  - Hypertrophic cardiomyopathy; single-cell RNA sequencing; vascular endothelial cells; biomarker; WGCNA

DO  - 10.32604/chd.2025.060406