Expression And Clinic Significance Of RON And Claudin-4in Bladder Transitional Cell Carcinoma

Objective: To determine the expression and clinic significance ofrecepteur d’origine naetais(RON) and Claudin-4in bladder transitional cellcarcinoma(TCCB) and investigate their possible role in progression andinvasion of TCCB.Methods: A total of36patients with pathological identified TCCBundergoing radical cystectomy in our department during March2010to May2011were recruited in this study.Their clinic data including pathologicalgrades, clinical stages, single and multiple foci, primary and recurrencetumor were collected.The expression of RON and Claudin-4in the tissuesamples of16normal bladder tissues and these36TCCB were tested byimmunohistochemical stain S-P, western blotting and reverse transcriptionpolymerase chain reaction(RT-PCR) at protein and mRNA levels,respectively. The relationships between RON and Claudin-4withpathological grades, clinical stages,sex,age,single and multiple foci, primaryand recurrence tumor were also analyzed. Results:1.In immunohistochemical stain S-P experiment,the expression ofRON in TCCB was significantly higher than that in normal bladdertissues(P=0.007),and significant differences were found in low grade andhigh grade differentiation,and in non-muscle invasion and muscle invasiontumors (P=0.029, P=0.041),but not in different sex,age, primary andrecurrence tumor and single and multiple foci (P>0.05); the expression ofClaudin-4in TCCB was significantly higher than that in normal bladdertissues(P=0.007),and significant differences were found in non-muscleinvasion and muscle invasion tumors (P=0.032),but not in low grade andhigh grade differentiation, different sex,age, primary and recurrencetumor,and single and multiple foci (P>0.05).2.In RT-PCR experiment, the expression of RON in TCCB wassignificantly higher than that in normal bladder tissues(P=0.000),andsignificant differences were found in low grade and high gradedifferentiation,and in non-muscle invasion and muscle invasion tumors(P=0.003, P=0.000),but not in different sex,age, primary and recurrencetumor and single and multiple foci (P>0.05); the expression of Claudin-4inTCCB was significantly higher than that in normal bladdertissues(P=0.003),and significant differences were found in non-muscleinvasion and muscle invasion tumors (P=0.018),but not in low grade andhigh grade differentiation, different sex,age, primary and recurrence tumor,and single and multiple foci (P>0.05).3. In western blotting experiment,the expression of RON in TCCBwas significantly higher than that in normal bladder tissues(P=0.000),andsignificant differences were found in low grade and high gradedifferentiation,and in non-muscle invasion and muscle invasion tumors(P=0.000, P=0.000),but not in different sex,age, primary and recurrencetumor and single and multiple foci (P>0.05); the expression of Claudin-4inTCCB was significantly higher than that in normal bladdertissues(P=0.000),and significant differences were found in non-muscleinvasion and muscle invasion tumors (P=0.000),but not in low grade andhigh grade differentiation, different sex,age, primary and recurrencetumor,and single and multiple foci (P>0.05).4.Both the protein and mRNA levels of RON and claudin-4werehigher in TCCB than those in normal bladder tissues,and were positivelycorrelated(r=0.560,P<0.05).Conclusion:1.The expression of RON in TCCB is significantly higher than that innormal bladder tissues both at protein and mRNA levels,and have asignificant difference in low grade and high grade differentiation,and innon-muscle invasion and muscle invasion tumors reveals that RON mayplay a positive role in the carcinogenesis, progression and invasion ofTCCB,and have a closely correlation to the extent of malignancy and the depth of invasion.2. The expression of Claudin-4in TCCB is significantly higher thanthat in normal bladder tissues both at protein and mRNA levels,and have asignificant difference in in non-muscle invasion and muscle invasion tumorsreveals that Claudin-4may play a positive role in the progression andinvasion of TCCB,and have a closely correlation to the depth of invasion.3.RON and Claudin-4up-regulate and positively correlated inTCCB,indicating that they may exert a positive regulatory effect on theprogression and invasion.