Investigating RNA m6 A-Related Biomarkers for Coronary Heart Disease through Transcriptomic Analysis of Peripheral Blood Mononuclear Cells
Objective By analyzing the MeRIP-seq and RNA-seq data of peripheral blood mononuclear cells(PBMCs)in coronary artery disease(CAD)cases and controls,determine potential m6A-associated biological indicators for the diagnosis of coronary heart disease,to provide new ideas for the prevention and treatment of CAD.Methods The expression of m6A(N6-methyladenosine)functional genes in the expression spectrum(GSE113079)of PBMCs in CAD cases and controls,were analyzed and m6A functional genes related to CAD were identified by LASSO and logistic regression.Subsequently,the MeRIP-seq and RNA-seq data of CAD case-control PBMCs and screened differentially methylated and differentially expressed genes were analyzed through various methods as potential CAD diagnostic markers.And then their efficacy was verified in public databases.Results In the expression spectrum data(GSE113079)of 141 CAD patients and healthy controls,there were significant differences in the expression levels of 22 m6A functional genes between the two groups.Receiver operating characteristic(ROC)curre analysis showed that the area under the curve(AUC)of the three-gene combination of ELAVL1,IGF2BP2,and METTL14 to identify CAD was 0.98.The GSE113079 data was combined with CAD MeRIP-seq and RNA-seq data for joint analysis,and 47 m6A target genes were obtained.By LASSO and logistic regression,the AUC of the ADM and SH2D2A gene combination in the CAD expression spectrum data(GSE113079)was 1,and the AUC in the peripheral blood expression spectrum data of myocardial infarction(GSE66360)was 0.79.In the atherosclerotic plaque expression spectrum data(GSE43292 and GSE28829),compared with the control group,the expression level of the ADM gene in the plaque was significantly increased(P＜0.05).Conclusion Through comprehensive analysis of the CAD expression spectrum database GSE113079,we identified the m6A functional gene(ELAVL1,IGF2BP2,and METTL14).Further analysis with MeRIP-seq and RNA-seq data led to the discovery of target genes ADM and SH2D2A.ADM is a potential CAD biomarker comfirmed by the validation set.
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