尿液中组织基质金属蛋白酶抑制剂对筛查膀胱癌的意义

Measurement of urinary TIMP-2:a possible method to diagnose bladder tumor

目的 初步探讨一种新的无创伤的筛查膀胱癌的方法。 方法 收集 5 0例膀胱癌患者术前 (17例Ta T1,2 1例T2 ,10例T3 ,2例T4 ;11例Ⅰ级 ,2 3例Ⅱ级 ,16例Ⅲ级和 11例正常人尿液 ,采用Westernblot半定量方法检测其中基质金属蛋白酶 2 (MMP 2 )、MMP 9和组织基质金属蛋白酶抑制剂 2 (TIMP)的表达。 结果 (1)正常人尿液中无MMP 2、MMP 9的表达 ,而TIMP 2表达阳性率为9 0 9% ;(2 )膀胱癌患者尿液中MMP 2、MMP 9、TIMP 2的阳性表达率分别为 18% ,12 % ,80 % ,且MMP 9的阳性率表达与肿瘤的病理分期和分级具有相关性 ;(3)半定量分析 ,MMP 2、MMP 9表达强度与患者分期分级无关 ,而在Ⅲ级和T4 期患者尿液中TIMP 2表达平均强度具有高于Ⅰ Ⅱ级和Ta T3 期患者的趋势。 结论 MMP 9在膀胱癌的侵袭过程中起着重要作用 ,通过检测尿液中TIMP 2的表达 。

Objective To measure the expression of urinary MMP-2, MMP-9 and TIMP-2 in 50 patients with bladder cancer and 11 normal volunteers to offer a new way to diagnose bladder carcinoma in clinic. Methods Urine samples were obtained from 50 patients with bladder cancers (17 T a-T 1, 21 T 2,10 T 3,2 T 4 ; 11 G 1,23 G 2,16 G 3) and 11 healthy volunteers. Samples were dialyzed and centrifuged, then the supernatant was stored at -70℃ before analysis. MMP-2, MMP-9 and TIMP-2 were detected in urine samples by means of western blot and image scan analysis. Results MMP-2 and MMP-9 were not detected in urine samples from normal volunteers, but TIMP-2 was observed about 909%. In urine samples from patients with bladder carcinoma, the positive expression rate of MMP-2, MMP-9 and TIMP-2 were 18%, 12%, 80% separately. MMP-9 positive expression rates were increased with grades and stages (P<005, χ2 test). Image analysis showed that the levels of TIMP-2 in grade Ⅲ and T 4 stage patients were higher than those in grade Ⅰ-Ⅱ and Ta-T 3 stage patients. Because the number of patients was small, statistical analysis was not performed. The levels of MMP-2 and MMP-9 howerer were not correlated with grades and stages. Conclusions The measurement of urinary TIMP-2 activity may be a convenient method for diagnosis of bladder carcinoma. The positive rate of urinary MMP-9 expression is associated with tumor stages and grades.