Expression Of MUC1 And MUC4 In Hepatocellular Carcinoma And Its Clinical Significance

Background and PurposeLiver cancer is a common malignant tumor in the world,with a high degree of malignancy and strong invasiveness.Mucins(MUC)are a kind of high molecular weight glycoproteins,which usually abnormally expressed in many tumors and affects the survival and prognosis of patients.Hepatocellular carcinoma(HCC)is the main pathological type of liver cancer at present,accounting for more than 90%cases.The main treatment is surgical resection,but its postoperative survival rate is low and lack of specific diagnosis and therapeutic targets.The purpose of this study was to investigate the expression of MUC in patients with HCC and normal liver tissues and the clinical significance of MUC expression.MethodsThe transcriptome data and clinical data of HCC in TCGA database were analyzed by UALCAN bioinformatics analysis platform.Then the differences of MUC expression between HCC and normal liver tissues were compared,and the survival of patients with HCC was analyzed in Kaplan-Meier plotter database.The MUC with significant differences in expression level and survival analysis were analyzed by gene variation analysis,immune infiltration analysis and gene association analysis,and the PPI network was screened and constructed.The core genes were further screened by the MCODE plug-in of Cytoscape software.The core genes were analyzed by GO functional annotation and KEGG enrichment analysis with R studio.ResultsAmong the 13 MUC analyzed,8 mucins(MUC1,MUC4,MUC5B,MUC6,MUC13,MUC15,MUC16,MUC20)were significantly different in normal liver tissues and HCC.Two mucins(MUC1,MUC4)were significantly associated with poor prognosis in HCC,with P value of 0.011,0.01,respectively.The high expression of MUC1 was significantly correlated with body weight,race,cancer stage and tumor histology,while the high expression of MUC4 was significantly correlated with lymphatic metastasis and tumor histology.Most of the MUC1 gene mutations were amplified mutations,and the survival prognosis of the patients was worse after the mutation,while most of the MUC4 gene mutations were missense mutations,which were not significantly related to the survival and prognosis of the patients.The expression of MUC1 was positively correlated with B cells,CD8~+T cells,CD4~+T cells,macrophages,neutrophils and dendritic cells in HCC,while the expression of MUC4was positively correlated with CD4~+T cells,macrophages and neutrophils in hepatocellular carcinoma.1154 genes were positively related to MUC1 expression and 403 genes were positively related to MUC4 expression.280 genes were expressed in both mucin-associated genes.The PPI network constructed by these 280genes consists of 268 nodes and 234 edges.Its core consists of 88 nodes and 148 edges.88core genes are enriched in cell adhesion,cell junction,protein binding,extracellular matrix receptor interaction,EGFR signal pathway,cancer signal pathway,etc.ConclusionsThe high expression of MUC1 and MUC4 is related to the poor prognosis of hepatocellular carcinoma.The signal pathways involved in MUC1 and MUC4 include cell adhesion,cell junction,extracellular matrix receptor interaction,EGFR signal pathway,cancer signal pathway,etc.MUC1 and MUC4 are expected to become new targets for diagnosis and therapeutic of HCC.