CXCR4和MMP-9在膀胱移行细胞癌中的表达

Expression of CXCR4 and MMP-9 in Bladder Transitional Cell Carcinoma Tissue

目的:探讨CXCR4与MMP-9在膀胱移行细胞癌中表达的相关性及其临床意义。方法:采用免疫组化SP法与半定量RT-PCR检测40例膀胱移行细胞癌组织及10例正常膀胱粘膜组织中CXCR4和MMP-9蛋白及mRNA的表达情况,分析膀胱移行细胞癌组织中CXCR4和MMP-9表达的相关性,分析二者与临床病理特征的关系。结果:膀胱移行细胞癌组织中CXCR4蛋白表达率为77.5%,mRNA相对含量为0.777±0.044;其中浸润深度达肌层者表达率为100%,mRNA相对含量为0.790±0.049;局限在粘膜下层者表达率为50%,mRNA相对含量为0.660±0.052;二者之间差异有统计学意义。MMP-9在膀胱移行细胞癌组织中的表达率为80.0%,mRNA相对含量为0.850±0.079,其中浸润深度达肌层者表达率为95.5%,mRNA相对含量为0.854±0.070,局限在粘膜下层者表达率为61.1%,mRNA相对含量为0.758±0.092,二者之间差异有统计学意义。膀胱移行细胞癌组织中CXCR4及MMP-9蛋白阳性表达呈正相关关系(γ=0.479,P<0.05)。MMP-9与肿瘤组织学分级有关,与患者的性别、年龄无关;而CXCR4的表达与肿瘤组织学分级及患者的性别、年龄均无关。结论:CXCR4和MMP-9表达与膀胱移行细胞癌的发生和浸润密切相关,通过干预CXCR4和MMP-9的活性可能成为治疗膀胱移行细胞癌的新靶点。

Objective： To investigate the expression and clinical significance of chemokine receptor CXCR4 and MMP-9 （matrix metalloproteinase-9） in human bladder transitional cell carcinoma （BTCC）. Methods： CXCR4 and MMP-9 protein and mRNA were detected in 40 formalin-fixed paraffin-embedded and fresh BTCC tissues and 10 normal bladder mucosal tissues by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction （RT-PCR） respectively. The association was analyzed between the expressions of CXCR4 and MMP-9, as well as their relationships to the clinicopathologic significance of BTCC. Results： The positive rate of expression of CXCR4 and MMP-9 protein and relative level of mRNA in BTCC tissues were significantly higher than those of the normal bladder mucosal tissues （CXCR4： 77.5% vs. 20%, 0.777± 0.044 vs. 0.623± 0.096; MMP-9： 80.0% vs. 20%, 0.850± 0.079 vs. 0.751± 0.049）. Further more, the positive rate of expression of CXCR4 and MMP-9 protein and relative level of mRNA in the muscle-in- vasive tumors were significantly higher than those of confined within submucosa too （CXCR4：100% vs. 50%, 0.790± 0.049 vs. 0.660± 0.052; MMP-9： 95.5% vs. 61.1%, 0.854± 0.070 vs. 0.758± 0.092）. The expression of CXCR4 protein was significantly positively correlated with that of MMP-9 protein （P〈0.05）. Nevertheless, the expression of CXCR4 among different histological grades did not have statistical significance while the expression of MMP-9 did. Both of the expression of CXCR4 and MMP-9 had no correlation with the sex and age of the patients. Conclusion： Our results suggest that CXCR4 and MMP-9 expression is highly correlated with the occurring and invasion of BTCC, and indicate that CXCR4 and MMP-9 could be a new efficient target to treat bladder cancer.