Related Experiment Video
Updated: Oct 27, 2025
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Identification of Underlying Hub Genes Associated with Hypertrophic Cardiomyopathy by Integrated Bioinformatics
Zetao Ma1,2, Xizhi Wang1, Qingbo Lv1
1Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310016, People's Republic of China.
Insights
This study identified five key genes involved in hypertrophic cardiomyopathy (HCM), a common inherited heart disease. These genes show potential as therapeutic targets and biomarkers for diagnosing and treating HCM.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Systems Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiovascular disease and a major cause of sudden cardiac death.
- Current effective treatments for HCM remain limited, highlighting the need for novel therapeutic strategies.
- Identifying key genes (hub genes) is crucial for discovering potential therapeutic targets and diagnostic biomarkers for HCM.
Purpose of the Study:
- To identify hub genes associated with hypertrophic cardiomyopathy (HCM) using gene expression datasets.
- To investigate the diagnostic value and expression levels of potential hub genes in HCM.
- To explore the role of identified hub genes in the development and progression of HCM.
Main Methods:
- Analysis of three Gene Expression Omnibus datasets for HCM, with merging of two datasets using the "sva" package.
- Weighted gene coexpression network analysis (WGCNA) to identify the key module significantly correlated with HCM.
- Identification of potential hub genes based on intramodular connectivity, followed by receiver operating characteristic (ROC) curve analysis for diagnostic value verification.
Main Results:
- A total of 455 differentially expressed genes (DEGs) were identified between normal and hypertrophic myocardium.
- The blue module from WGCNA was identified as the key module positively correlated with HCM, with enrichment analysis pointing to extracellular matrix, fibrosis, and neurohormone pathways.
- Five hub genes (FRZB, COL14A1, CRISPLD1, LUM, and sFRP4) were identified, showing significant upregulation in HCM patients and transverse aortic constriction (TAC) mouse models, with LUM and sFRP4 protein expression also increased in TAC mice.
Conclusions:
- This research successfully identified five hub genes implicated in the pathogenesis of hypertrophic cardiomyopathy (HCM).
- These identified hub genes demonstrate significant potential for development as therapeutic targets for HCM.
- The study suggests these five genes may also serve as valuable biomarkers for the diagnosis and management of HCM.
Background:
Considered as one of the major reasons of sudden cardiac death, hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease. However, effective treatment for HCM is still lacking. Identification of hub gene may be a powerful tool for discovering potential therapeutic targets and candidate biomarkers.
Methods:
We analysed three gene expression datasets for HCM from the Gene Expression Omnibus. Two of them were merged by "sva" package. The merged dataset was used for analysis while the other dataset was used for validation. Following this, a weighted gene coexpression network analysis (WGCNA) was performed, and the key module most related to HCM was identified. Based on the intramodular connectivity, we identified the potential hub genes. Then, a receiver operating characteristic curve analysis was performed to verify the diagnostic values of hub genes. Finally, we validated changes of hub genes, for genetic transcription and protein expression levels, in datasets of HCM patients and myocardium of transverse aortic constriction (TAC) mice.
Results:
In the merged dataset, a total of 455 differentially expressed genes (DEGs) were identified from normal and hypertrophic myocardium. In WGCNA, the blue module was identified as the key module and the genes in this module showed a high positive correlation with HCM. Functional enrichment analysis of DEGs and key module revealed that the extracellular matrix, fibrosis, and neurohormone pathways played important roles in HCM. FRZB, COL14A1, CRISPLD1, LUM, and sFRP4 were identified as hub genes in the key module. These genes showed a good predictive value for HCM and were significantly up-regulated in HCM patients and TAC mice. We also found protein expression of LUM and sFRP4 increased in myocardium of TAC mice.
Conclusion:
This study revealed that five hub genes are involved in the occurrence and development of HCM, and they are potentially to be used as therapeutic targets and biomarkers for HCM.
Related Concept Videos
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...