# Construction of a competitive endogenous RNA network and identification of potential regulatory axes in hypertrophic cardiomyopathy

## TL;DR

This study identifies key genes and RNA networks involved in hypertrophic cardiomyopathy, offering new insights into its causes and potential biomarkers.

## Contribution

The novel ceRNA network and three hub genes (CD163, FCER1G, CYP2J2) linked to immune function in HCM are newly identified.

## Key findings

- Three hub genes (CD163, FCER1G, CYP2J2) were identified with high diagnostic value in HCM.
- A ceRNA network revealed five regulatory axes involving lncRNAs, miRNAs, and hub genes.
- Immune infiltration analysis showed dysregulation of macrophages, T cells, and dendritic cells in HCM.

## Abstract

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous cardiovascular disease, the pathogenesis of which remains unclear. In this study, we aimed to explore potential biomarkers and competitive endogenous RNA (ceRNA) network in HCM using integrated bioinformatics analysis.

Three mRNA expression datasets relevant to HCM, along with one long non-coding RNA (lncRNA) dataset, were retrieved from the Gene Expression Omnibus database. Differential expression analysis was conducted using the “limma” package. Hub genes were subsequently explored through an integrated bioinformatics approach, which included weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network construction, and feature selection methods. The expression levels and diagnostic accuracy of the candidate hub genes were validated in GSE141910. A ceRNA regulatory network was constructed by predicting interactions using miRDB, miRWalk, DIANA-LncBase, and lncRNASNP2 databases. Finally, immune cell infiltration analysis was performed to elucidate the immune landscape in HCM.

We intersected genes from three sources: 642 differentially expressed genes (DEGs) from GSE36961, 1,612 DEGs from GSE160997, and 2,930 genes from key WGCNA modules, yielding 162 common genes. A PPI network of these genes revealed 78 nodes, from which three pivotal clusters were identified. Feature selection methods converged on three hub genes (CD163, FCER1G, and CYP2J2), each demonstrating high diagnostic value. A ceRNA network was constructed, revealing five potential regulatory axes: SNHG1/miR-543/CD163, MEG8/miR-543/CD163, ZFAS1/miR-2110/FCER1G, SNHG14/miR-5001-5p/FCER1G, and TTN-AS1/miR-6740-3p/CYP2J2. Immune infiltration analysis indicated notable dysregulation of multiple immune cells in HCM, and the identified hub genes showed significant correlations with key immune subsets, including macrophages, regulatory T cells, and activated dendritic cells.

Through integrated analysis, three hub genes linked to immune function (CD163, FCER1G, and CYP2J2) were discerned, and a corresponding ceRNA network was delineated. These results contribute to a renewed understanding of the pathogenic mechanisms in HCM.