Significance of RNA N6-methyladenosine modulators and immune infiltration in the diagnosis and subtyping of ischemic stroke

Abstract

Abstract RNA N6-methyladenosine (M6A) regulators play an important part in a variety of cellular physiological and pathological processes. However, the part of m6A modulators in ischemic stroke remains unclear.Six important m6A regulators were selected from the gene expression repertoire GSE22255, GSE16561 and GSE37587 datasets by differential gene expression analysis between healthy people and ischemic stroke patients.A two models were constructed, and the RF model was used to screen six significant m6A regulators (Methyltransferase-like 3, Leucine Rich Pentatricopeptide Repeat Containing, Cbl Proto-Oncogene Like 1, Wilm's tumor 1 -associated protein, ELAV Like RNA Binding Protein 1 and AlkB Homolog 5, RNA Demethylase) to predict the risk of ischemic stroke.Based on 6 candidate M6A modulators, a nomogram model was established to analyze the clinical benefit of ischemic patients.Using consensus clustering, ischemic stroke patients were separated among m6A-cluster subtypes (cluster A and cluster B) based on selected significant m6A regulators. A PCA algorithm was applied to compute m6A scores for each sample to quantify m6A-cluster subtypes.The m6A scores of ischemic stroke patients in group B were lower than those in group A.At the same time, this research also found that ischemic stroke patients with low gene expression of ALKBH5, ELAVL1, LRPPRC and METTL3 improved immune cell infiltration, and ischemic stroke patients with high gene expression of CBLL1 and WTAP improved immune cell infiltration.In conclusion, m6A regulators play an important part in the disease process of ischemic stroke. The study of m6A-cluster subtypes is beneficial to direct future immunotherapy tactics for ischemic stroke.