Abstract
Sepsis in children is a syndrome associated with organ dysfunction caused by immune dysregulation of inflammatory responses in children. According to the latest data, nearly50 million people have been diagnosed with sepsisand nearly10 million have died. M6A methylation has been reported to be associated with sepsis-associated inflammatory response[2],however, the molecular biological mechanism underlying the diagnosis and treatment of m6A related genes in children remains unclear. It provides a new way for clinical incidence prediction and molecular biology diagnosis, and further guides clinical treatment.The GEO database chip dataset GSE66099 was downloaded and annotated by platform files. The m6A related genes were extracted. The data were standardized by R language limma package.181 children with septic shock,18 children with sepsis were selected as sepsis group,47 normal childrenand30 children with common SIRS were selected as control group. The difference of m6A gene expression between control group and sepsis group was analyzed by correlation test. The importance score of m6A-related genes in sepsis was obtained by cross-validation error of random forest tree method, disease-related characteristic genes were screened, the influence of core difference genes on sepsis incidence was analyzed, and nomogram was drawn to predict patient incidence. The number of disease characteristic genes was determined by LASSO model, ROC curve was drawn, and related genes were selected for further analysis. Cluster analysis was performed on sepsis patients according to the expression of biomarkers, and difference and correlation analysis were performed on immune infiltration. Among the first 13 differentially expressed genes, DIGFBP1 and IGFBP2 were up-regulated in sepsis patients, while METTL3, MITTL14, MERTTL16, RBM15, RBM15B, CBLL1, YTHF2, HNRNPC, LRPPRC, ELAVL1 and FTO were down-regulated in sepsis patients. In addition, ROC curve analysis showed that HNRNPC, LRPPRC, FTO andELAVL1 were characteristic genes of the disease. We also identified two m6A genotypes and two differential genotypes. Based on differential gene expression, nine m6A gene expressions were statistically different in a 2-typing pattern, with differences associated with immune infiltration. m6A methylation modification may play a potentially important role in the diagnosis,immune infiltration and treatment of sepsis in children. HNRNPC may be one of the potential molecular markers for predicting sepsis in children. Typing based on m6A gene expression has potential implications for the treatment of sepsis in children.