尿液BLCA-1与BLCA-4检测对膀胱癌早期无创性诊断和复发监测的价值

The value of combined detection of BLCA-1 and BLCA-4 in urine for early diagnosis and surveillance for bladder cancer

目的研究尿液BLCA-1与BLCA-4检测对中国人群膀胱癌的诊断和复发监测的价值,初步探讨其对不同分期、分级的膀胱癌诊断效能的差异。方法制备BLCA-1和BLCA-4多克隆抗体,间接ELISA法检测尿液中BLCA-1及BLCA-4水平,研究其与患者临床病理参数的相关性。免疫组织化学法检测各分期、分级膀胱癌组织标本中BLCA-1及BLCA-4的表达情况,分析比较各组间的差异。结果膀胱癌患者尿液中BLCA-1与BLCA-4的水平均显著高于正常对照组(P<0.000 1)和良性泌尿系统疾病患者(P<0.000 1)。Cut-off值为0.000 9OD/μg时,BLCA-1检测膀胱癌的敏感度达92.7%,特异度达92.9%。Cut-off值取0.000 17OD/μg时,BLCA-4检测膀胱癌的敏感度为97.4%,而特异度为100%。因受研究病例数较少的限制,未发现BLCA-1本身或联合BLCA-4检测对监测膀胱癌复发有价值。尿液BLCA-1和BLCA-4水平在各分期、分级膀胱癌患者间均无显著差异,但肌层浸润性膀胱癌患者尿液中BLCA-4的表达显著高于非肌层浸润性膀胱癌患者(P=0.018)。膀胱癌组织中BLCA-1的表达随肿瘤分级、分期的进展而逐渐升高,呈正相关(P<0.001),BLCA-1在肌层浸润性膀胱癌组织中的水平显著高于非肌层浸润性膀胱癌组(P<0.001),膀胱癌组织中BLCA-4的表达水平与膀胱癌的分期(P=0.837 7)和分级(P=0.489 1)均不相关。结论尿液中BLCA-1与BLCA-4均为具有高度特异性及敏感性的膀胱肿瘤标志物,尿液BLCA-1联合BLCA-4检测对膀胱癌复发的预测价值仍需进一步探讨。

Objective To evaluated the value of combined detection of BLCA-1 and BLCA-4 in urine for early diagnosis and surveillance of bladder cancer. Methods Monocolonal antibodies of BLCA-1 and BLCA-4 were generated and indirect ELISA was used to detect their level in urine. Ciin- icopathological parameters were studied for the association with BLCA-1 and BLCA-4. Urine samples from patients with bladder cancer of various stages and grades, and the cases with other benign uro- logical disorders （as controls） were collected and tested. Immunohistochemical method was used to detect tissue samples from patients with bladder cancer of various stages and grades. Results U- rine BLCA-1 levels were significantly higher than control. When the cut-off value of BLCA-1 was set at 0.000 90μg, which yielded a sensitivity of 92.7% and a specificity of 92.9% for bladder canc- er, and when the cut-off value of BLCA-4 at 0.000 17 ODμg, yielded a sensitivity of 97.4% and a specificity of 100%. Owing to the limited cases, the value of detection of BLCA-1 alone or the com- bination of BLCA1 and BLCA-4 for the surveillance of recurrence bladder cancer were fail to confirm. Conclusions Detection of urinary BLCA-1 and or BLCA-4 can provide excellent tumor markers for early diagnosis of bladder cancer with high specificity and sensitivity. However, the predictive value of detection of BLCA-1 alone or combination with BLCA-4 for recurrent bladder cancer recurrence need to be further studied.