Diagnosis, clustering, and immune cell infiltration analysis of m6A-related genes in patients with acute myocardial infarction—a bioinformatics analysis

Abstract

Background: Accurate myocardial infarction (AMI) is one of the leading causes of mortality worldwide.N6-methyladenosine (m6A) modification plays an important role in the development of cardiac remodeling and the cardiomyocyte contractile function. The aim of this study is to analyze the m6A-related molecular biological mechanisms of AMI in terms of accurate diagnosis and prognosis. Methods:The platform data and probe data of the GSE66360 data set were downloaded. The differential analysis was conducted by combining the m6A-related gene expression. Thereafter, a diagnostic model was established using the random-forest method. The diagnostic accuracy of the diagnostic models was assessed by using the area under the receiver operating characteristic (ROC) curve (AUC). Next, the patients with AMI were clustered by unsupervised machine learning using the R software. Finally, an immune cell clustering analysis for each cluster was conducted to determine the correlations between m6A-related gene expression and the infiltration amount of the immune cells. The case and control groups were not matched in terms of demographics.Results: The GSE6636 data set comprised 99 participants (49 patients with AMI and 50 without in control group). The differential analysis identified 10 m6A-related genes: 5 writers [Methyltransferaselike 3 (METTL3), Methyltransferase-like 14 (METTL14), Wilms tumor 1-associated protein (WTAP), Zinc Finger CCCH-Type Containing 13 (ZC3H13), and Casitas B-lineage proto-oncogene like 1 (CBLL1)],4 readers [YT521-B homology domain-containing family 3 (YTHDF3), Fragile X mental retardation type 1 (FMR1), YT521-B homology-domain-containing protein 1 (YTHDC1), and insulin-like growth factor binding protein 3 (IGFBP3)] and 1 eraser [fat mass and obesity associated (FTO) gene]. The Mean Decrease Gini (MDG) values of these 10 genes were greater than 2. The FTO, WTAP, YTHDC1, IGFBP3, and CBLL1were included in the model with a C index of 0.842. METTL3, ZC3H13, WTAP, and CBLL1 were highly expressed in Type A, and YTHDF3 was highly expressed in Type B.Conclusions: A diagnostic model of AMI was established based on the genes of FTO, WTAP, YTHDC1, IGFBP3, and CBLL1. Additionally, 2 molecular subtypes were successfully identified from the abovementioned gene. Our findings could provide a novel method for the accurate diagnosis of AMI.

Comprehensive Analysis of N6-Methyladenosine RNA Methylation Regulators in the Diagnosis and Subtype Classification of Acute Myocardial Infarction

“…Both the expression of genes related to m6A as well as the infiltration of immune cells were distinctly diverse between the two subtypes. It is important to note that the m6A-related genes were, on average, expressed at a higher level in Type A AMI compared to Type B AMI [ 35 ]. Additionally, immune cell infiltration was more common in Type A AMI.…”

Identification of key genes and lncRNAs based on M6A methylation regulators and Ferroptosis related genes for the slow flow/no reflow phenomenon

“…Besides, GSE66360 microarray including 49 AMI and 50 control samples were obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) and used as a validation set. In addition, 27 M6A methylation regulators (MMRs) containing 10 writers (METTL3, METTL14, METTL16, WTAP, VIRMA, ZC3H13, RBM15, RBM15B, CBLL1, and KIA1499), 2 erasers (ALKBH5 and FTO), and 15 readers (YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, HNRNPC, FMR1, LRPPRC, HNRNPA2B1, IGFBP1, IGFBP2, IGFBP3, RBMX, ELAVL1, and IGF2BP1) were obtained from published articles [14,16]. 149 Ferroptosis related genes (FRGs) were sourced from the published article [17].…”

“…N6-methyladenosine (m6A) modi cation is one of the common epigenetic modi cations, accounting for more than 80% of all RNA modi cations [13]. Previous studies have found that m6A methylation is widely involved in the development of various types of cardiovascular diseases [14] and may provide a reference to explore the occurrence of slow ow/no re ow. In addition, Ferroptosis is one of the forms of programmed cell death that acts differently from apoptosis, necrosis, and autophagy, with the main mechanism being that unsaturated fatty acids from the cell membrane are catalyzed in the presence of divalent iron or ester oxygenases, which activate lipid peroxidation and induce cell death.…”

Identification MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 as the potential immune-related key genes involved in ischaemic cardiomyopathy by random forest and nomogram

“…Moreover, compared with other methods, the random forest method is more effective in identifying key genes significantly associated with disease. [ 17 ]. Recently, as a widely applied analytical method, CIBERSORT has often been used to study the immune cell infiltration pattern in diseases based on RNA sequencing or microarray data and to evaluate the infiltrated proportion of 22 immune cells in each sample [ 18 ].…”