The Expression And Clinical Significance Of EPS15 In Primary Hepatocellular Carcinoma

BackgroudHepatocellular carcinoma?HCC?is a kind of common malignancy oncoma.It has the characteristics of concealed onset,rapid proliferation,difficult early diagnosis and strong drug resistance^[1].Various complications associated with hepatocellular carcinoma bring more risks to patients,for example,patients with portal vein tumor thrombosis may have worse liver function,lower treatment receptive ability and worse prognosis than patients without portal vein tumor thrombosis^[2],In addition,they may be at risk of massive hemorrhage and hemorrhagic shock caused by portal hypertension.As we all know,the occurrence,development and prognosis of tumor are caused by many different reasons,have complicated processes and uncertainties influence factors.It has important and profound significance for the diagnosis and treatment of cancer to explore the mechanisms relevanted of tumors.EPS15 is a protein tyrosine kinase substrate of EGFR?epidermal growth factor receptor?.It participates in the endocytosis and secretion of EGFR^[3],regulates the intracellular transport as a multifunctional adaptor protein.By this way,EPS15 can down-regulate the transmission of growth factor signals,and affect the clinical characteristics of some tumors,such as grading,staging,prognosis,etc.^[4].In recent years,foreign studies have found that EPS15 is abnormally expressed in some tumor cells and tissues,and its abnormal expression may be related to the formation and development of tumors^[5].In this study,the expression of EPS15 in hepatocellular carcinoma cells was preliminarily discussed,and the relationship between the expression of EPS15 and the prognosis of patients with hepatocellular carcinoma and its effect on the migration of hepatocellular carcinoma cells was analyzed.ObjectiveTo investigate the expression and clinical significance of epidermal growth factor receptor protein tyrosine kinase substrate 15?EPS15?in hepatocellular carcinoma?HCC?and its effect on cell migration.MethodsUse tissue microarray and immunohistochemistry to analyze the expression of EPS15 in hepatocellular carcinoma.The expression of EPS15 in HCC tissues and normal tissues was analyzed by using UALCAN?http://ualcan.path.uab.edu/?in the cancer genome mapping?TCGA?;the relationship between EPS15 expression and survival time of HCC patients was analyzed by online survival analysis software called Kaplan-Meier plotter;down-regulate EPS15 by siRNA transfection,then use Western blot to detect the expression of EPS15 protein,and Transwell test was used to detect the effect of down-regulation of EPS15 on the migration of HCC cells.Results1.The results of immunohistochemistry:The expression of EPS15 in hepatocellular carcinoma tissues was significantly higher than that in normal tissues.The difference was significant?P<0.001?.2.The results of data analysis on tissue microarray:There's no difference in the expression of EPS15 in HCC patients with different gender?x²=0.193,P=0.660?,tumor size?x²=0.638,P=0.424?,HBV infection?x²=2.324,P=0.127?,TNM stages?x²=0.743,P=0.389?,and pathological grades?x²=0.550,P=0.458?.The online software UALCAN?http://ualcan.path.uab.edu/?was used to analyze the expression of EPS15 in hepatocellular carcinoma tissues of stage I^IV and grade I^IV in TCGA database.The results showed that the expression level of EPS15 in stage III hepatocellular carcinoma tissues was higher than that in stage I hepatocellular carcinoma tissues,the expression level of EPS15 in grade III hepatocellular carcinoma tissues was higher than that in grade I hepatocellular carcinoma tissues,with significant difference?P<0.001?,but there is no significant difference between other grades or stages of hepatocellular carcinoma tissues.3.Kaplan-Meier plotter analysis of TCGA database results:Among the 365patients with hepatocellular carcinoma in TCGA database,the overall survival time of patients with high expression of EPS15 was shorter than that of patients with low expression of EPS15?P<0.01?,that is,patients with high expression of EPS15 had poor prognosis.4.Western blot results:Compared with NC group,siRNA successfully down-regulated the expression of EPS15 in hepatocellular carcinoma cells,which proved the effectiveness of siRNA.5.Transwell results:After the expression of siRNA-EPS15,the number of cells migrating to the inferior chamber through the filter membrane decreased significantly?P<0.05?,indicating that down-regulation of EPS15 decreases the migration ability of hepatocellular carcinoma cells.Conclusion1.The expression of EPS15 in hepatocellular carcinoma is higher than that in normal tissues.2.There is no significant difference in EPS15 expression among patients with different sex,tumor size,history of HBV infection.The expression level of EPS15 in stage III hepatocellular carcinoma tissues was higher than that in stage I hepatocellular carcinoma tissues,and in stage III hepatocellular carcinoma tissues was higher than that in grade I hepatocellular carcinoma tissues.3.The patients with high expression of EPS15 have shorter overall survival time and poor prognosis.4.Down-regulation of EPS15 expression in hepatocellular carcinoma cells decreases cell migration.