Published online May 26, 2022. doi: 10.4330/wjc.v14.i5.282
Peer-review started: December 14, 2021
First decision: January 25, 2022
Revised: February 19, 2022
Accepted: April 26, 2022
Article in press: April 26, 2022
Published online: May 26, 2022
Processing time: 155 Days and 6.4 Hours
Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated.
To investigate the candidate genes and pathways involved in DCM patients.
Two expression datasets (GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between the DCM patients and healthy individuals were identified using the R package “linear models for microarray data.” The pathways with common DEGs were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network (PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs (miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT.
In total, 97 DEGs (47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in “response to growth factor,” “extracellular matrix,” and “extracellular matrix structural constituent.” KEGG pathway analysis indicated that the DEGs were mainly enriched in “protein digestion and absorption” and “interleukin 17 (IL-17) signaling pathway.” The PPI network suggested that collagen type III alpha 1 chain (COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells.
COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM.
Core Tip: As the most common cause of heart failure, the diagnosis and therapy for dilated cardiomyopathy (DCM) are still unsatisfactory because of its indistinct pathogenesis and specific biomarkers. Thus, we comprehensively utilized the microarray data from the Gene Expression Omnibus database to uncover the biomarker and mechanisms underlying DCM development. Collagen type III alpha 1 chain and collagen type I alpha 2 chain, which are regulated by hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM through the acute inflammatory response and interleukin 17 signaling pathway. These biomarkers and mechanisms need to be further studied.