The Role Of N6-methyladenosine Regulatory Genes On The Prognosis,Progression And Tumor Micro-environment Of Liver Hepatocellular Carcinoma

Objective: To explore the effect of m6 A regulatory genes on the prognosis of Liver Hepatocellular Carcinoma(LIHC).Methods: RNA-Seq and clinical data were downloaded from The Cancer Genome Atlas(TCGA)database.The differential expression of methylated regulatory genes between tumor tissue m6 A para-carcinoma tissue samples was analyzed by wilcoxon test.Using Lasso-Cox regression analysis to construct a LIHC risk prognostic model of m6 A methylation regulatory genes.The median risk score was used to divide LIHC patients into high-risk and low-risk groups.The Kaplan-Meier survival analysis was carried out in both groups.The ROC curve was used to evaluate the sensitivity and specificity of the prediction model.Univariate and multivariate COX regression were used to verify whether the model was an independent prognostic factor affecting the LIHC.The CIBERSORT algorithm was used to calculate the immune abundance of leukocyte subtypes in each HCC sample and to predict their correlation with m6 A risk models.Result: In this study,a total of 18 m6 A methylation regulatory genes were analyzed,16 of which were differentially expressed.Five m6 A methylation regulatory genes(including METTL3,IGF2BP3,YTHDF2,YTHDF1 and ZC3H13)were identified by the Lasso-Cox regression analysis.The immune risk score of each sample was calculated,and the median value of the immune risk score was used as the dividing value,then all the samples were divided into two groups: high-risk and low-risk.Compared with the low-risk group,the overall survival rate of the high-risk group was significantly lower(P<0.0001).The AUC values in the ROC curves of 1.3 and 5 years are 73.7%,69.7% and65.4% respectively,which indicates that the prediction model is effective.Univariate and multivariate Cox regression were used to test the effectiveness of the model.The HR value Cox multi-factor regression analysis was 3.1(p<0.001).The analysis of immune infiltration showed that the high risk group promoted the progression of liver cancer by reducing the abundance of B cells and NK cells in the immune microenvironment of liver cancer and increasing the abundance of M2 macrophages.Conclusion: The m6 A methylation regulatory genes can construct a risk prognosis model to predict the OS of LIHC patients.