A Comparative Analysis Of The Expression Of EREG In Clinical Renal Carcinoma And Leukemia Patients And Its Effects On Malignant Behavior In Human Renal Carcinoma Cell 786-O

Background: EREG(Epiregulin)is a epidermal regulatory protein that is a self-secreting or paracrine regulator.As a member of the epidermal growth factor(EGF)family,it binds to EGFR in the ErebB receptor tyrosine kinase family to phosphorylate EGFR and thus play a variety of biological functions,it was found and isolated from the mouse cell culture medium.A variety of studies have shown that abnormal expression of EREG is closely related to the development of malignant behavior of tumors,but no studies have been reported in clinical specimens of renal cell carcinoma and leukemia.This study was designed to investigate the relationship between EREG and clinicopathological factors and its value in the diagnosis and prognosis of cancer by studying the expression level of EREG in clinical samples of renal cell carcinoma and leukemia,and thus can help to study the early diagnosis of cancer of kidney cancer and leukemia.Objective: 1.EREG expression levels in clinical tissue samples of ccRCC patients and its correlation with progression of RCC.2.Measuring EREG expression levels in bone marrow mononuclear cells of patients with different leukemia and its correlation with leukemia occurs.3.The influence of recombinant protein EREG on the proliferation,migration and invasion abilities in vitro of human renal carcinoma786-O cells.Methods: 1.Clinical samples of 55 patients with ccRCC were collected and itscorresponding normal normal tissues,57 leukemia patients and 13 normal donors samples were also collected.2.Using the real-time fluorescent quantitative PCR methods to detection the expression level of EREG in clinical samples.3.According to the detailed clinical and pathological information of patients,the correlation between the expression level of EREG in patients with RCC and leukemia and clinicopathological parameters was analyzed by statistical analysis.4.The statistical analysis of EREG in leukemia patients with different clinical types of differential expression of comparative analysis and the changing of EREG levels in the initial and complete remission of leukemia patients.5.The effect of recombinant human EREG protein on the proliferation ability in vitro of 786-O cells was detected by MTT assay.6.The effect of recombinant human EREG protein on the migration and invasion abilities in vitro of 786-O cells was detected by Transwell chamber method.Results: 1.EREG in clear cell renal carcinoma of the overall low expression and its compared with the normal adjacent tissue decreasing by 30.1 %(P = 0.0017),among them,36 cases were low expression,15 cases were high expression,4 cases had no obvious change.2.The expression level of EREG was significantly correlated with the TNM staging of patients with ccRCC(P = 0.019),but there had no correlation with clinicopathological parameters such as sex,age,side and tissue type(P > 0.05).3.Compared with normal donor samples,the expression level of EREG in leukemia patients was significantly lower,the overall level decreased by 48.7 %(P =0.0038);Differences expression of EREG in leukemia patients were significantly associated with age(P = 0.020),and there were not associated with gender(P > 0.5);The expression of EREG in patients with chronic myeloid leukemia(CML)was45.4 %(P = 0.0027)lower than that in normal donor groups,there were 28 cases lower expression and 4 cases overexpressed;The expression of EREG in patients with acute lymphoblastic leukemia(ALL)was 46.0 % lower than that in the normal group(P = 0.0267),there were 11 cases lower expression,5 cases overexpressed and 1 case no obvious changing;The expression of EREG in patients with acute myeloid leukemia(AML)was 67.1 % lower than that in the normal group(P = 0.0026),there were 7 cases lower expression and 1 cases overexpressed.4.The level of EREGexpression in patients with CML and AML patients increased with CR compared with the initial status of patients with leukemia,and P values are respectively 0.049,0.0393.5.The effect of human recombinant EREG on the proliferation in vitro of786-O cells was not obvious and the migration and invasion ability in vitro of 786-O cells were inhibited.Conclusions: 1.In clinical samples detection,EREG mRNA expression in RCC and leukemia patients was lower than that in the normal group.2.In patients with renal cell carcinoma,the differential expression of EREG was not significantly correlated with clinicopathological parameters such as gender,age,side and tissue type,but there was significantly correlated with pathological stage.3.The differential expression of EREG mRNA was not associated with gender in patients with leukemia,but there was significantly associated with age.4.Patients with chronic myeloid leukemia and acute myeloid leukemia after complete remission,EREG can be used as a potential indicator of detection of molecular factors when its levels rised.5.Human recombinant EREG protein had no effect on the proliferation ability in vitro of RCC786-O cells and inhibited the migration and invasion ability of cells.