Research Paper Volume 15, Issue 5 pp 1475—1495
Identification MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 as the potential immune-related key genes involved in ischaemic cardiomyopathy by random forest and nomogram
- 1 Cardiology Department, Hunan Provincial People’s Hospital, Furong, Changsha 410000, Hunan, China
- 2 Clinical Research Center for Heart Failure in Hunan Province, Furong, Changsha 410000, Hunan, China
- 3 Institute of Cardiovascular Epidemiology, Hunan Provincial People’s Hospital, Furong, Changsha 410000, Hunan, China
- 4 The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Furong, Changsha 410000, Hunan, China
Received: November 27, 2022 Accepted: February 11, 2023 Published: February 27, 2023
https://doi.org/10.18632/aging.204547How to Cite
Copyright: © 2023 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The immune molecular mechanisms involved in ischaemic cardiomyopathy (ICM) have not been fully elucidated. The current study aimed to elucidate the immune cell infiltration pattern of the ICM and identify key immune-related genes that participate in the pathologic process of the ICM. The differentially expressed genes (DEGs) were identified from two datasets (GSE42955 combined with GSE57338) and the top 8 key DEGs related to ICM were screened using random forest and used to construct the nomogram model. Moreover, the “CIBERSORT” software package was used to determine the proportion of infiltrating immune cells in the ICM. A total of 39 DEGs (18 upregulated and 21 downregulated) were identified in the current study. Four upregulated DEGs, including MNS1, FRZB, OGN, and LUM, and four downregulated DEGs, SERP1NA3, RNASE2, FCN3 and SLCO4A1, were identified by the random forest model. The nomogram constructed based on the above 8 key genes suggested a diagnostic value of up to 99% to distinguish the ICM from healthy participants. Meanwhile, most of the key DEGs presented prominent interactions with immune cell infiltrates. The RT-qPCR results suggested that the expression levels of MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 between the ICM and control groups were consistent with the bioinformatic analysis results. These results suggested that immune cell infiltration plays a critical role in the occurrence and progression of ICM. Several key immune-related genes, including the MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 genes, are expected to be reliable serum markers for the diagnosis of ICM and potential molecular targets for ICM immunotherapy.
Abbreviations
ICM: Ischaemic cardiomyopathy; DEGs: Differentially expressed genes; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; DO: Disease Ontology; HF: Heart failure; CAD: Coronary artery disease; Tregs: T-lymphocytes; GEO: Gene Expression Omnibus; FC: Fold change; CC: Cell composition; BP: Biological processes; MF: Molecular functions; DCA: Decision curve analysis; ROC: Receiver operator characteristic; NYHA: New York Heart Association; CI: Confidence interval; AUC: Area under the curve; FRZB: Frizzled-related protein; HCM: Hypertrophic cardiomyopathy; OGN: Osteoglycin; SLRP: Small leucine-rich proteoglycan; LUM: Lumican; MNS1: Meiosis-specific nuclear structural 1; SERPINA3: Serpin family A member 3; FCN3: Ficolin-3.