The Expression And Significance Of E2F1 And EGR-1 In Renal Clear Cell Carcinoma

Objectives: Renal cell carcinoma(RCC) accounts for about 2% to 3 % of adult malignancies,and renal clear cell carcinoma(RCCC) is the most common malignancy amongst RCC.25% of patients has been found neoplasm metastasis,when they are diagnosed with RCCC.Patients with metastatic RCC are not sensitive to chemoradiotherapy,and immune therapy and molecular targeted therapy have low efficiency for them.Uncontrolled cell cycle regulation is one of the important reasons for the occur and development progress of tumours,meanwhile cell cycle regulation requires a variety of transcription factors interact with each other.Transcription factor E2F1 and early growth response gene-1(EGR-1) are closely related to the occurrence, development and metastasis of a wide variety of tumours,but there is no report of the expression of E2F1 and EGR-1 in RCCC.This study aims to observe the expression of E2F1 and EGR-1 in RCCC group and control group,and analyze their association with clinical stages,pathological grades and patient’s gender,age,and discuss the role of E2F1 and EGR-1 in the occur and development progress of RCCC.Methods:1 We selected 48 cases of RCCC surgery specimens in the department of Urological Surgery,He Bei medical university second affiliated hospital from April 2013 to May 2014(confirmed by pathology),meanwhile we chose 28 cases of adjacent normal renal tissue as control group(more than 4 cm away from the RCCC tissue,confirmed by pathology).All patients before surgery were not given radiotherapy, chemotherapy,cytokine therapy and molecule targeted therapy.All specimens were divided into two groups,one group was fixed by 10% neutral buffered formalin,then embedded in paraffin and serially 4μm cut,another group was placed in-80 refrigerator℃.2 Immunohistochemistry was used to detect the expression of E2F1 protein and EGR-1 protein in control group and renal clear cell carcinoma group.The expression of m RNA of E2F1 and EGR-1 was detected with RT-PCR in control group and renal clear cell carcinoma group,and integral absorbance values of E2F1 and EGR-1 m RNA represented the result.3 To keep a simultaneously record of age,gender,clinical stages and pathological grades of 48 cases of renal clear cell carcinoma patients.We used immunohistochemistry to detect the expression of E2F1 protein and EGR-1 protein in tissues of 48 cases of clear cell renal cell carcinomas,and analyzed their association with clinical stages,pathological grades and patient’s gender,age,and the expression correlativity between E2F1 and EGR-1 in 48 cases of renal cell carcinoma tissues.4 Data analysis was done with SPSS13.0 statistical software.We analyzed the difference positive expression rate of E2F1 and EGR-1 between in control group and RCCC group by χ2 test or Fisher’s exact probability test.We used χ2 test or Fisher’s exact probability test to compare the expression of E2F1,EGR-1 with the clinicopathologic charter of patients in RCCC group, and analyzed the correlativity of E2F1 and EGR-1 expression in RCCC group by Spearman rank correlation analysis.The integral absorbance values of E2F1 and EGR-1 m RNA were represented by mean ± standard deviation( sx ±).P<0.05 was considered statistically significant.Results:1 Immunohistochemistry method showed that the protein expression of E2F1 mainly distributed in the nucleus, and it was up-regulated in RCCC group(75%)compared to control group(32.1%)(P<0.05).The protein expression of EGR-1 mainly distributed in the nucleus,the positive expression rate of EGR-1 was higher in RCCC group(79.2%) than that in control group(35.7%)(P<0.05). RT-PCR method showed that integral absorbance values of E2F1 were 0.2628±0.0656 and 0.1225±0.0237 in RCCC group and control group.RCCC group were significantly higher than control group(P<0.05).The integral absorbance values of EGR-1 were 0.2788±0.0893 and 0.1279±0.0266 in RCCC groups and control groups.RCCC groups were significantly higher than control groups(P<0.05).2 48 cases of RCCC patients consisted of 31 cases of male and 17 female,aged 45 to 76 years old.We divided the specimens into pathological grades: 10 cases of high differentiation group,19 cases of median differentiation group and 19 cases of low differentiation group according to the Fuhrman grade established in 1997 by WHO.We divided the specimens into clinical stage:Ⅰ10 cases,Ⅱ18 cases,Ⅲ16 cases and Ⅳ4 cases according to the TNM staging system for kidney cancer established by 2010 AJCC.There was positive correlation between E2F1 and EGR-1 in RCCC group(r=0.533,P<0.01).The expression of E2F1 in RCCC tissues in the clinical stage Ⅲand Ⅳwas higher than that in the stage Ⅰ and Ⅱ(χ2=7.314,P<0.01),and in the pathological grades low differentiation group was higher than that in median differentiation group and high differentiation group(χ2=6.534,P<0.05).The expression of EGR-1 in RCCC tissues in the clinical stage Ⅲand Ⅳwas higher than that in the stageⅠ and Ⅱ(χ2=5.211, P<0.05),and in the pathological grades low differentiation group was higher than that in median differentiation group and high differentiation group(χ2=8. 276,P<0.01).However,there was not association between expression of E2F1,EGR-1 and sex, age of patient(P>0.05).Conclusion:1 The expression of E2F1 and EGR-1 in RCCC group was higher than that in control group.2 Clinical stage and pathological grades of RCCC were positively correlated with the expression of E2F1 and EGR-1 in RCCC tissue but not with sex, age of patient.3 There was positive correlation between E2F1 and EGR-1 in RCCC group.4 E2F1 and EGR-1 may become valuable markers of renal clear cell carcinoma growth,which may be significant to studying RCCC pathogenesis.