RON及Claudin-4在人膀胱移行细胞癌中的表达及临床意义

Expression and clinic significance of RON and claudin-4 in bladder transitional cell carcinoma

目的研究RON(recepteur d’origine naetais)及Claudin-4在人膀胱移行细胞癌(bladder transitional cell car-cinoma,TCCB)中的表达及临床意义,探讨两者在肿瘤中的作用。方法收集人正常膀胱移行上皮组织标本16例,膀胱移行细胞癌标本36例,按照病理分级、临床分期、性别、年龄、单发与多发、初发与复发进行分组,分别用Western blot和RT-PCR检测RON、Claudin-4蛋白和mRNA的表达,分析两者与TCCB的病理分级、临床分期、性别、年龄、单发与多发、初发与复发间的关系。结果①TCCB组中的RON表达水平明显高于正常膀胱移行上皮组织(P=0.000),TCCB组低级别与高级别、非肌层浸润(T1)与肌层浸润(T2～4)间表达差异有统计学意义(P=0.003,P=0.000),而在年龄、初发与复发、单发与多发组间表达差异无统计学意义(P>0.05)。②TCCB组中的Claudin-4表达水平明显高于正常膀胱黏膜组织(P=0.003),TCCB组T1与T2～4间表达差异有统计学意义(P=0.018),而在低级别与高级别、年龄、初发与复发、单发与多发组间表达差异无统计学意义(P>0.05)。③TCCB组RON与Claudin-4蛋白及基因表达水平均呈增高趋势,且两者呈正相关(r=0.560,P<0.05)。结论 TCCB组中RON与Claudin-4蛋白及基因表达上调提示两者在TCCB的发展和浸润中起促进作用,且RON与Claudin-4在TCCB中呈正相关。

Objective To determine the expression and clinic significance of recepteur d＇origine naetais（RON） and claudin-4 in bladder transitional cell carcinoma（TCCB） and investigate their possible role in progression and invasion of TCCB.Methods A total of 36 patients with pathological identified TCCB undergoing radical cystectomy in our department during March 2010 to May 2011 were recruited in this study.Their clinical data including pathological grades,clinical stages,single and multiple foci,primary and recurrence tumor were collected.The expression of RON and claudin-4 in the tissue samples of 16 normal bladder tissues and these 36 TCCB were tested by Western blotting and reverse transcription polymerase chain reaction（RT-PCR） at protein and mRNA levels,respectively.The relationships between RON and claudin-4 with pathological grades,clinical stages,sex,age,single and multiple foci,primary and recurrence tumor were also analyzed.Results The expression of RON in TCCB was significantly higher than in normal bladder tissues（P=0.000）,and significant differences were found in low-grade and high grade differentiation,and in non-muscle invasion and muscle-invasive tumors（P=0.003,P=0.000）,but not in different sex,age,primary and recurrence tumor,and single and multiple foci（P0.05）.The expression of claudin-4 in TCCB was significantly higher than in normal bladder tissues（P=0.003）,and significant difference was found between non-muscle invasion and muscle-invasive tumors（P=0.018）,but not in low-grade and high grade differentiation,sex,age,primary and recurrence tumor,and single and multiple foci（P0.05）.Both the protein and mRNA levels of RON and claudin-4 were higher in TCCB than those in normal bladder tissues,and were positively correlated（r=0.560,P0.05）.Conclusion RON and Claudin-4 are up-regulated and positively correlated in TCCB,indicating that they may exert a positive regulatory effect on the progression and invasion.