Association Analysis Of Methylation-driven-gene Expression And Prognosis Analysis Of Hepatocellular Carcinoma Using Bioinformatics Analysis

Objective:Hepatocellular carcinoma is the most common primary liver cancer and one of the most common malignant tumors.But we haven’t found the mechanism of its occurrence.The imbalance of methylation and demethylation may be one of the mechanisms which causinng primary liver cancer.Exploration of the relationship between methylation and demethylation maybe provides new ideas for the occurrence,new prevention and treatment of tumors.was Using bioinformatics to analyze and screen methylation-driven genes of liver cancer tissues,can explore the relationship between the differential expression of the methylation-driven genes which belongs liver cancer,explore the causes and mechanisms of liver cancer,and analyze the clinical data of liver cancer patients.Prognostic analysis was performed to provide theoretical basis for guiding prognostic staging and exploring new therapeutic targets for liver cancer.Method:The expression of methylation-driven genes in liver cancer tissues and control tissues in the Gene Expression Omnibus and The Cancer Genome Atlas(TCGA)liver cancer database was analyzed using the R language Limma software package,and differentially expressed genes(DEGs)were found.The Methyl Mix program package was used to analyze the degree of gene methylation,and the Wilcoxon rank sum test method was used to find the methylation driver genes that were different between liver cancer tissues and control tissues.Gene Ontology(GO)functional enrichment analysis of liver cancer methylation-driven genes was performed using the software DAVID.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis was performed on liver cancer methylation driver genes using the database KOBAS 3.0.Prognostic differences between the two groups were analyzed using the Kaplan-Meier method.We analyze the significance of liver cancer methylation driver genes in the clinical characteristics of patients and their relationship with the prognosis of patients.Results:1.There was 2516 genes differentially expressed in tumor and control samples,of which1290 genes were down-regulated and 1226 genes were up-regulated.8 DNA methylation-driven genes were identified by methylation differences and gene expression differences.The 8 hypermethylation driver genes were: ASPDH,ANK3,NR4A1,MT1XP1,BHMT,CXCL2,NAT2,and CRP.2.Through the GO function analysis of 8 liver cancer methylation-driven genes,it was found that there are 6 processes involved in biological,mainly in cell adhesion,immune response,classical activation pathway of complement,redox and so on.Protein binding,calcium ion binding,extracellular matrix structural components,helical structure,and phosphatidylcholine production are among the five molecular functions involved.There are16 components involved in cytology,mainly involved in extracellular matrix,adipocyte differentiation,serosa,extracellular area,lysosomal membrane,etc.3.Through the analysis of the KEGG pathway of the methylation driver gene in liver cancer,we found 30 pathways,mainly involving four categories: signaling pathway(PI3K-Akt signaling pathway,AGE-RAGE signaling pathway),cell adhesion(cell adhesion molecule,local adhesion),anabolism(phenylalanine,tyrosine,tryptophan,riboflavin biosynthesis and metabolism),pathways in immune-related diseases(Th1 and Th2 cell differentiation,B cell receptor signaling pathways),antigen processing and presentation,etc.)4.Univariate survival analysis was performed on the expression of 8 hypermethylation driver genes.Among them,3 genes(ASPDH,BHMT,CXCL2)had statistically significant,with p values of 0.00067,0.0095,and 0.0041,respectively.The lower the expression of ASPDH,BHMT,and CXCL2,the worse the prognosis.The effect of ANK3,NR4A1,NAT2 and CRP on prognosis was not statistically significant.Conclusion:1.ASPDH,BHMT,and CXCL2 are potential tumor markers for apparent induction of HCC.2.ASPDH,BHMT,CXCL2 are closely related to the occurrence and development of HCC.3.ASPDH,BHMT,CXCL2 are related to the prognosis of patients with HCC,and the patients with low expression have poor prognosis.4.The expression and methylatio of ASPDH,BHMT and CXCL2 were significantly different,showing a significant negative correlation...