Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database

Abstract

RNA N6-methyladenosine (m6A) regulators play important roles in a variety of biological functions. Nonetheless, the roles of m6A regulators in childhood asthma remain unknown. In this study, 11 significant m6A regulators were selected using difference analysis between non-asthmatic and asthmatic patients from the Gene Expression Omnibus GSE40888 dataset. The random forest model was used to screen five candidate m6A regulators (fragile X mental retardation 1, KIAA1429, Wilm’s tumor 1-associated protein, YTH domain-containing 2, and zinc finger CCCH domain-containing protein 13) to predict the risk of childhood asthma. A nomogram model was established based on the five candidate m6A regulators. Decision curve analysis indicated that patients could benefit from the nomogram model. The consensus clustering method was performed to differentiate children with asthma into two m6A patterns (clusterA and clusterB) based on the selected significant m6A regulators. Principal component analysis algorithms were constructed to calculate the m6A score for each sample to quantify the m6A patterns. The patients in clusterB had higher m6A scores than those in clusterA. Furthermore, we found that the patients in clusterA were linked to helper T cell type 1 (Th1)-dominant immunity while those in clusterB were linked to Th2-dominant immunity. In summary, m6A regulators play nonnegligible roles in the occurrence of childhood asthma. Our investigation of m6A patterns may be able to guide future immunotherapy strategies for childhood asthma.

m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma

“…Moreover, in another study on childhood asthma found that m6A regulators also played a crucial role, and screened five candidate m6A regulators (FMR1, KIAA1429, WTAP, YTHDC2 and ZC3H13) to predict the risk of childhood asthma. 17 However, there is still a blank in the field of severe asthma and m6A. Besides, recent studies have shown that m6A modification plays an important role in innate immune response and adaptive immune response, [30][31][32] it has been proved that it plays an important role in tumour immune microenvironment, [33][34][35] so we believe that in the pathogenesis of severe asthma, there are similar to the occurrence of m6A modification, and this was confirmed in this study.…”

“…15 It can even explain the potential mechanism of immune regulation in some diseases. Although more and more evidence shows the regulatory role of m6A in immune response 16 and also proves the diagnostic significance of m6A regulatory pattern in childhood asthma, 17 there is still a gap in the research on severe asthma and m6A. Therefore, In this study, we systematically evaluated the m6A regulator-mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma.…”

N6-Methyladenosine Methylomic Landscape of Lung Tissues in Murine Acute Allergic Asthma

“…This study analyzed the gene expressions of m6A enzymes in the peripheral blood mononuclear cells of children (average age, 8.4 years) with asthma and found two different expression patterns of the m6A enzymes that were associated with the immune responses of T helper cells (Th1 and Th2). Besides, the degree of immune infiltration was higher in patients with an upregulated methylase WTAP gene expression compared to that in patients with a downregulated expression ( 39 ). Another intensive research reported on the potential mechanism of m6A modification in the Th2 immune response of asthma ( 40 ).…”

“…Thus far, only two studies have directly investigated the relationship between asthma and m6A modification. One of them showed that m6A enzymes may have a role in the pathogenesis of asthma through bioinformatics analysis of the public dataset from the GEO database ( 39 ). This study analyzed the gene expressions of m6A enzymes in the peripheral blood mononuclear cells of children (average age, 8.4 years) with asthma and found two different expression patterns of the m6A enzymes that were associated with the immune responses of T helper cells (Th1 and Th2).…”

Identification of Type 2-pediatric Asthma Based on Single-cell Transcriptomic Analysis

“…Asthma is a heterogeneous disease, and transcriptome sequencing is often used to study the pathogenesis of asthma and the e cacy of drug intervention in asthma [15][16][17]. Owing to the heterogeneity of asthma, traditional transcriptome sequencing methods based on blood or tissue samples obtain macroscopic results of the cell population, showing the average expression level of the same gene in all cells, rather than the differences between individual cells of the same gene and its role in the pathogenesis of the disease.…”