膀胱癌组织中uPA和MMP-9表达与肿瘤微血管生成关系的研究

Expression of uPA and MMP-9 in Bladder Cancer and its Relationship with Tumor Angiogenesis

目的研究膀胱癌组织中尿激酶型纤维蛋白溶解酶原激活剂(uPA)和基质金属蛋白酶9(MMP-9)表达及与肿瘤微血管生成之间的关系。方法运用免疫组化S-P法检测66例膀胱癌组织和19例膀胱良性病变组织(对照组)中uPA和MMP-9的表达,同时分析不同uPA和MMP-9表达状态下,膀胱癌组织微血管密度(MVD)的变化。结果膀胱癌组织中uPA和MMP-9的表达率分别为72.7%(48/66)和75.8%(50/66),高于对照组中uPA和MMP-9的表达率(分别为26.3%,5/19;和4.21%,8/19),差异有统计学意义(P值分别为<0.001和0.005);浸润性癌中uPA和MMP-9的表达均强于浅表性癌,差异有统计学意义(P值分别为0.046和0.004);低中分化癌中uPA的表达强于高分化癌,差异有统计学意义(P=0.003),MMP-9的表达与肿瘤病理分级无关;uPA表达与MMP-9表达呈显著正相关关系(rs=0.269,P=0.029)。将膀胱癌分为3组,A组为uPA/MMP-9两者均为弱表达(n=14),B组为uPA/MMP-9两者之一为弱表达(n=19),C组为uPA/MMP-9两者均为弱表达(n=33)。3组MVD计数分别为89.9±23.8,71.8±22.0和62.6±31.9,A组MVD计数高于C组,差异有统计学意义(P=0.003)。结论uPA和MMP-9的表达与膀胱癌的浸润和肿瘤微血管生成密切相关,VPA和MMP-9的表达具有协同性,二者的联合检测可作为判断膀胱癌预后的分子标记。

Objective To investigate the expression of urokinase- type plasminogen activator （uPA） and matrix metalloproteinase 9 （MMP-9） in bladder cancer and its relationship with tumor angiogenesis Method The expression ofuPA and MMP-9 in 66 cases of bladder cancer and 19 cases of bening urologic disease （as control） was determined with S- P assay, and the microvessei density （MVD） was compared among different expression states of UPA and MMP- 9 in bladder cancer tissues. The pnsitive expression rates of uPA and MMP- 9 in 66 cases of bladder cancer were 71.2% （47/66） and74.2% （49/ 66）, respectively, which were significantly higher than those in control group （26.3%, 5/19, P 〈 0.001 ; and 42.1%, 8/19, P = 0.009, respectively）; Invasive bladder cancer showed a higher reactivity for both uP A and MMP- 9 than superficial bladder cancer （P =0.046 and 0.004, respectively）; simultaneously, poorly and moderately differentiated cancer also showed a higher reactivity for uPA than well - differentiated cancer （ P = 0.003）, but the expression of MMP- 9 in bladder cancer showed no relationship with tumor grade; There was a significant correlation with the coexpression of uPA and MMP- 9 （ rs = 0.269, P =0.029）. The bladder cancer tissues were subdivided into 3 groups： tissues with both overexpression of uPA and MMP - 9 as group A （ n = 14）, tissues with one overexpressionof uPA and MMP- 9 as group B （n = 19）, tissues with both weak expression of uPA and MMP - 9 as group C （ n = 33） .The MVD counts of group A, B and C were 89.9 ± 23.8, 71.8 ± 22.0 and 62.6 ± 31.9, respectively.The MVD counts of group A were significantly higher than those of group C （ P = 0.003 ）. Conclusion The overexpression of uPA and MMP - 9 in bladder cancer is closely correlated with tumor invasion and angiogenesis.The overexpression and coexpression of uPA and MMP- 9 in bladder cancer indicates that the combined detection of the two biomarkers can be used as useful biomarkers for the prognosis of bladder caliper.