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

摘要

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 9 OD/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 17 OD/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.Clinicopathological 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 urological 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 Urine BLCA-1 levels were significantly higher than controls.When the cut-off value of BLCA-1 was set at 0.000 9 OD/μg, which yielded a sensitivity of 92.7% and a specificity of 92.9% for bladder cancer, and when the cut-off value of BLCA-4 at 0.000 17 OD/μg, 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 combination of BLCA-1 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.