Exploration and validation of hub genes and pathways in the progression of hypoplastic left heart syndrome via weighted gene co-expression network analysis

Abstract Background Despite significant progress in surgical treatment of hypoplastic left heart syndrome (HLHS), its mortality and morbidity are still high. Little is known about the molecular abnormalities of the syndrome. In this study, we aimed to probe into hub genes and key pathways in the progression of the syndrome. Methods Differentially expressed genes (DEGs) were identified in left ventricle (LV) or right ventricle (RV) tissues between HLHS and controls using the GSE77798 dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed and key modules were constructed for HLHS. Based on the genes in the key modules, protein–protein interaction networks were conducted, and hub genes and key pathways were screened. Finally, the GSE23959 dataset was used to validate hub genes between HLHS and controls. Results We identified 88 and 41 DEGs in LV and RV tissues between HLHS and controls, respectively. DEGs in LV tissues of HLHS were distinctly involved in heart development, apoptotic signaling pathway and ECM receptor interaction. DEGs in RV tissues of HLHS were mainly enriched in BMP signaling pathway, regulation of cell development and regulation of blood pressure. A total of 16 co-expression network were constructed. Among them, black module (r = 0.79 and p value = 2e−04) and pink module (r = 0.84 and p value = 4e−05) had the most significant correlation with HLHS, indicating that the two modules could be the most relevant for HLHS progression. We identified five hub genes in the black module (including Fbn1, Itga8, Itga11, Itgb5 and Thbs2), and five hub genes (including Cblb, Ccl2, Edn1, Itgb3 and Map2k1) in the pink module for HLHS. Their abnormal expression was verified in the GSE23959 dataset. Conclusions Our findings revealed hub genes and key pathways for HLHS through WGCNA, which could play key roles in the molecular mechanism of HLHS.

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Exploration and Validation of Hub Genes and Pathways in the Progression of Hypoplastic Left Heart Syndrome via Weighted Gene Co-Expression Network Analysis

10.21203/rs.3.rs-105782/v1 ◽

2020 ◽

Author(s):

Xuelan Liu ◽

Honglei Shang ◽

Bin Li ◽

Liyun Zhao ◽

Ying Hua ◽

...

Keyword(s):

Network Analysis ◽

Signaling Pathway ◽

Hypoplastic Left Heart Syndrome ◽

P Value ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Hub Genes ◽

Black Module ◽

Left Heart Syndrome ◽

Key Pathways

Abstract Objective: Despite significant progress in surgical treatment of hypoplastic left heart syndrome (HLHS), its mortality and morbidity are still high. Little is known about the molecular abnormalities of the syndrome. In this study, we aimed to probe into hub genes and key pathways in the progression of the syndrome.Methods: Differentially expressed genes (DEGs) were identified in left ventricle (LV) or right ventricle (RV) tissues between HLHS and controls using the GSE77798 dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed and key modules were constructed for HLHS. Based on the genes in the key modules, protein-protein interaction (PPI) networks were conducted, and hub genes and key pathways were screened. Finally, the GSE23959 dataset was used to validate hub genes between HLHS and controls.Results: 88 and 41 DEGs were identified for LV and RV tissues between HLHS and controls, respectively. DEGs in LV tissues of HLHS were distinctly involved in heart development, apoptotic signaling pathway and ECM receptor interaction. DEGs in RV tissues of HLHS were mainly enriched in BMP signaling pathway, regulation of cell development and regulation of blood pressure. A total of 16 co-expression network were constructed. Among them, black module (r=0.79 and p-value=2e-04) and pink module (r=0.84 and p-value=4e-05) had the most significant correlation with HLHS, indicating that the two modules could be the most relevant for HLHS progression. We identified five hub genes in the black module (including Fbn1, Itga8, Itga11, Itgb5 and Thbs2), and five hub genes (including Cblb, Ccl2, Edn1, Itgb3 and Map2k1) in the pink module for HLHS. Their abnormal expression was verified in the GSE23959 dataset. Conclusion: Our findings revealed hub genes and key pathways for HLHS through WGCNA, which could play key roles in the molecular mechanism of HLHS.

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Transcription repression and blocks in cell cycle progression in hypoplastic left heart syndrome

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.91494.2007 ◽

2008 ◽

Vol 294 (5) ◽

pp. H2268-H2275 ◽

Cited By ~ 16

Author(s):

Katheryn Gambetta ◽

Mohamad K. Al-Ahdab ◽

Michel N. Ilbawi ◽

Nahidh Hassaniya ◽

Madhu Gupta

Keyword(s):

Cell Cycle ◽

Real Time ◽

Hypoplastic Left Heart Syndrome ◽

Expression Patterns ◽

Atrial Septum ◽

Left Heart ◽

Rt Pcr ◽

Hypoplastic Left Heart ◽

Molecular Abnormalities ◽

Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is characterized by abnormally developed atrial septum and a severe underdevelopment of the left side of the heart. Despite significant advances in its surgical management, little is known about the molecular abnormalities in this syndrome. To gain molecular insights into HLHS, expression profiling by gene-chip microarray (Affymetrix U133 2.0) and by real-time RT-PCR was performed in the atrial septum of patients diagnosed with HLHS and compared with age-matched non-HLHS patients. Hierarchical clustering of all expressed genes with a P < 0.01 of all tissue samples showed two main clusters, one of HLHS and the other of non-HLHS, suggesting different expression patterns by the two groups. Net affix followed by real-time RT-PCR analysis identified the differentially expressed genes to be those involved in chromatin remodeling, cell cycle regulation, and transcriptional regulation. These included remodeling factors, histone deactylase 2 and SET and MYND domain containing 1; transcription factors, FoxP1, and components of the calcineurin-nuclear factor of activated T cells signaling pathway; and cell cycle regulators, cyclin-dependent kinase (CDK)-4, phosphatase and tensin homolog, and p18. Since these factors play essential roles in heart growth and development, the abnormal expression pattern suggests that these molecules may contribute to the pathogenesis of HLHS.

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