Expression Of Bmi-1, AEG-1 As High Expressed Genes Of Bladder Cancer And Tumor-suppressor Genes FHIT In Bladder Transitional Cell Carcinoma And Their Corelationship

Objective:Based on the early stage of the experiments,we confirmed the Bmi- 1 gene closely relationship with bladder transitional cell carcinoma.To study the expression of Bmi-1, AEG-1 and FHIT in transitional cell carcinoma of bladder, and their relationship with the development and metastasis of bladder cancer, And then discusses the relationship between the three genes, to seek further their role in bladder transitional cell carcinoma whether there is a common way to provide experimental basis.Methods:We collected 46 cases of transitional cell carcinoma of bladder and 10 cases of the normal bladder mucous membrane tissues which were confirmed by pathological specimens during 2010~2014. m RNA levels were detected by real-time PCR, protein expression were measured by Western-Blot and immunohistochemistry. Data were performed by SPSS 17.0 soft ware. Chi-square test and t-test were used to analyze the relationship between protein expression and stage, grade and lymphatic metastasis. Spearman rank correlation analysis was used to study the correlation ship of protein expression.Results:(1)Real-Time PCR showed that Bmi-1、AEG-1m RNA levels were lower and FHIT m RNA level was higher in normal tissues. But in transitional cell carcinoma of bladder, Bmi-1、AEG-1m RNA levels were higher and FHIT m RNA level was lower. m RNA level of Bmi-1, AEG-1 and FHIT were significantly correlated with tumor grade and lymphatic metastasis. Bmi-1、AEG-1m RNA were increased while FIHT m RNA was decreased as the increase of tumor grade and lymphatic metastasis. There’s no relationship between m RNA level of Bmi-1, AEG-1 and FHIT and tumor staging.(2) Western-blot analysis showed that Bmi-1、AEG-1protein levels were higher in transitional cell carcinoma of bladder, especially in higher grade and lymphatic metastasis group. FIHT protein level was decreased as the up regulation of Bmi-1、AEG-1.(3) Immunohistochemical results showed that Bmi-1、AEG-1、FHITprotein levels in normal bladder tissue and in the bladder cancer.A 10% of normal bladder tissue showed positive expression of Bmi-1, while 60.87% in transitional cell carcinoma of bladder. 20% of normal bladder tissue showed positive expression of AEG-1, while 73.91% in transitional cell carcinoma of bladder. 90% of normal bladder tissue showed positive expression of FHIT, while 43.48% in transitional cell carcinoma of bladder.B In Tis-T1, positive rate of Bmi-1 was 55.56%, while 68.42% in T2-T4. In Tis-T1, positive rate of AEG-1 was 66.67%, while 84.21% in T2-T4. In Tis-T1, positive rate of FHIT was 48.15%, while 36.84% in T2-T4.C In lower grade group, positive rate of Bmi-1 was 37.50, while 86.36% in higher grade group. In lower grade group, positive rate of AEG-1 was 58.33, while 90.91% in higher grade group. In lower grade group, positive rate of FHIT was 58.33, while 27.28% in higher grade group.D In non-lymphatic metastatic group, positive rate of Bmi-1 was 43.33%, while 93.75% in lymphatic metastatic group. In non-lymphatic metastatic group, positive rate of AEG-1 was 60%, while 100% in lymphatic metastatic group. In non-lymphatic metastatic group, positive rate of FHIT was 56.67%, while 18.75% in lymphatic metastatic group.There was no difference between Bmi-1, AEG-1 and FHIT expression and clinical stage. And there were significantly differences between Bmi-1, AEG-1 and FHIT expression and grades, lymphatic metastasis. These results were consistent with real-time PCR and western-blots.(4) Expression of Bmi-1was positively correlated with AEG-1(r=0.741). Expression of Bmi-1 and AEG-1were negatively correlated with FIHT(R=-0.645 and-0.667 respectively)Conclusions:(1) Expression of Bmi-1, AEG-1 and FHIT in TCCB were related to tumor grade and lymphatic metastasis, and unrelated to tumor stage. Bmi-1、AEG-1protein levels were increased while FIHT protein level was decreased as the increase of tumor grade and lymphatic metastasis.(2) Bmi-1 may have synergistic effects with AEG-1 and FIHT during the development and metastasis of TCCB.(3) We proved that AEG-1 and FHIT are closely associated with bladder cancer, and Bmi-1 may have the effect of upregulation of AEG-1 and downregulation of FHIT.(4) loss or low expression of FHIT may become a diagnostic indicator of bladder cancer.