Dysfunctional network of hub genes in hypertrophic cardiomyopathy patients

Shan Wu; Iqtidar Ud Din; Faisal Mahmood Sadiq; Mostafa A Abdel-Maksoud; Muhammad Haris; Ayman Mubarak; Mohamed A Farrag; Sumaiah Alghamdi; Sally Almekhlafi; Muhammad Akram; Guangyao Li

Dysfunctional network of hub genes in hypertrophic cardiomyopathy patients

Am J Transl Res. 2022 Dec 15;14(12):8918-8933. eCollection 2022.

Authors

Affiliations

¹ Wuhu No. 1 People's Hospital Wuhu 241000, Anhui, China.
² Department of Cardiology, Nowshera Medical College Nowshera, Pakistan.
³ Punjab Institute of Mental Health Lahore, Pakistan.
⁴ Department of Botany and Microbiology, College of Science, King Saud University P.O. 2455, Riyadh 11451, Saudi Arabia.
⁵ Department of Anatomy, Nowshera Medical College Nowshera, Pakistan.
⁶ Faculty of Medicine & Allied Medicine, Nishtar Medical College Multan, Pakistan.
⁷ The Second People's Hospital of Wuhu, Department of Gastrointestinal Surgery Wuhu 241000, Anhui, China.
⁸ Wuhu Hospital Affiliated to East China Normal University Wuhu, Anhui, China.

PMID: 36628247
PMCID: PMC9827312

Abstract

Background: Considering it is one of the major causes of sudden cardiac arrest, the proper management of hypertrophic cardiomyopathy (HCM) is essential. However, efficient treatment options for this disease are still lacking. The discovery of HCM-associated hub genes may help in diagnosis and offer a reliable tool for developing effective therapeutic strategies.

Methods: We examined HCM-based gene expression datasets (GSE36961) from the Gene Expression Omnibus (GEO) database for the identification of differentially expressed genes (DEGs), PPI network development, module screening, and shortlisting of hub genes via GEOR2, STRING, and Cytoscape. Moreover, we also used another HCM-based gene expression dataset (GSE32453) for the expression validation of hub genes. Following this, we constructed the lncRNA-cricRNA-miRNA-mRNA regulatory network after retrieving information from the miRTarBase, miRDB, and MiRcode databases. Finally, we used DAVID to perform functional and pathway analysis of the hub genes.

Results: From GSE36961, a total of the 262 most significant DEGs, including 162 down-regulated and 76 up-regulated, were identified between HCM patients and normal individuals. Among these DEGs, a total of 10 significantly down-regulated DEGs, including cluster of differentiation 14 (CD14), beta2 Integrin Gene (ITGB2), C1q subcomponent subunit B (C1QB), Cluster of Differentiation 163 (CD163), Hematopoietic Cell-Specific Lyn Substrate 1 (HCLS1), Arachidonate 5-Lipoxygenase Activating Protein (ALOX5AP), Pleckstrin (PLEK), Complement C1q C Chain (C1QC), Fc fragment Of IgE receptor Ig (FCER1G), and tyrosine kinase binding protein (TYROBP), were shortlisted as the hub genes. Pathway enrichment analysis showed that the identified hub genes were involved in the dysregulation of some diverse pathways in HCM patients. Such as, Pertussis, Complement and coagulation cascade, Legnionellosis, Asthma, Staphylococcus aureus infection, etc. Lastly, we also explored hub genes' regulatory 2 MicroRNAs (miRNAs, has-mir-7-5p and has-mir-27a-3p), one Long non-coding RNAs (lncRNA, OIP5-AS1-201), and one Circular RNA (cricRNA, CDR1as) via lncRNA-cricRNA-miRNA-mRNA regulatory network.

Conclusion: Our study revealed that ten hub genes (CD14, ITGB2, C1QB, CD163, HCLS1, ALOX5AP, PLEK, C1QC, FCER1G, and TYROBP) are involved in the development and progression of HCM. These genes can potentially be used as biomarkers and therapeutic targets for HCM patients.

Keywords: Hypertrophic cardiomyopathy; biomarker; hub genes; miRNAs; therapeutic target.