Construction and validation of prognostic model of hepatocellular carcinoma based on epigenetic factors

Objective:To explore the targeting relationship between miRNA and epigenetic factors related to the prognosis of hepatocellular carcinoma(HCC),and to identify the potential impact of miRNA targeted epigenetic factors on the prognosis of HCC.Methods:The mRNA and miRNA sequencing data of all HCC samples were downloaded from the tumor Genome Atlas(TCGA)database,and the R program was used to analyze the difference of the sequencing data.The data of survival time,survival status and differential expression of miRNA were combined,and the risk score model of miRNA was constructed by univariate and multivariate Cox regression.The miRNA target genes and all the corresponding Epigenetic factors were predicted,and the differentially expressed Epigenetic factors(DEEFs)were screened.Then,the regulatory network of miRNA targeting deefs was established,the apparent factors in the network were enriched and analyzed,and the core genes in the protein-protein interaction(PPI)network and selection network were constructed.Finally,the relationship between the apparent factors and the prognosis of patients was analyzed and verified by Kaplan Meier(K-M)method.Results:305 differentially expressed miRNAs were identified using EDGE algorithm.After Cox analysis,hsa-miR-139-5p,hsa-miR-101-3p and hsa-miR-7-5p(miR-139-5p,miR-101-3p and miR-7-5p)were finally screened as the Overall survival of HCC patients(Overall survival,OS).In addition,34 DEEFs targeted by miRNAs were identified,among which EZH2,PKM,HJURP and CHEK1 had a significant impact on the survival of hepatocellular carcinoma.Conclusion:In this study,we successfully established a prognostic model of hepatocellular carcinoma miRNA-targeted epigenetics,and screened out epigenetic factors that are significantly related to the prognosis of hepatocellular carcinoma.It provides new potential prognostic biomarkers and therapeutic targets for HCC treatment,and lays a theoretical foundation for the follow-up basic research of HCC.