尿液载脂蛋白-A1在膀胱癌诊断中的应用及其临床意义

Clinical significance and application value of apolipoprotein-A1 in urine for the diagnosis of bladder cancer

目的:探讨尿液载脂蛋白-A1(Apo-A1)在膀胱癌诊断中的临床价值。方法:收集膀胱癌患者及健康人尿液标本行双向电泳,根据电泳图谱挑选表达差异显著的蛋白进行质谱鉴定分析;免疫印迹验证后ELISA方法检测尿液中差异蛋白的表达水平,绘制受试者工作特征(ROC)曲线以确定该蛋白对膀胱癌诊断的最佳工作点,并进行大样本临床验证试验,计算相应的特异度和灵敏度;并分析差异蛋白检测与尿脱落细胞检查联合应用诊断膀胱癌的临床价值。结果:尿液双向电泳结合质谱分析结果显示,Apo-A1在膀胱癌组呈现显著的高表达趋势。ELISA结果表明Apo-A1在膀胱癌组含量明显高于健康对照组,差异有统计学意义(P<0.01);以19.21μg/L为临界点,可将膀胱癌患者与非膀胱癌患者较好区分,灵敏度为88.3%,特异度为83.7%。将Apo-A1检测与尿脱落细胞学检查联合应用,能够明显提高膀胱癌诊断的灵敏度。结论:Apo-A1有可能是膀胱癌诊断的一个生物学标志物,具有潜在的临床应用价值。

Objective：To investigate the clinical value of apolipoprotein-A1（Apo-A1）in urine for the diagnosis of bladder cancer.Method：Urine samples from patients with bladder cancer and health controls were separated individually by two-dimensional electrophoresis（2-DE）and one of the differentially expressed proteins was identified by mass spectrometry（MS）,which was further confirmed by western blot.Enzyme-linked immunosorbent assay（ELISA）was used to quantify the protein in the two groups.A receiver operating characteristic（ROC）curve was generated to identify the optimal operating point.The results were verified clinically,and the sensitivity and specificity were calculated.The combined diagnostic value of the protein in urine and cytology were further explored.Result：Urine proteins from patients with bladder cancer and healthy controls were resolved by 2-DE,and Apo-A1 as the most differentially expressed protein was identified by MS and confirmed by immunoblot.Apo-A1 expressed significantly higher in bladder cancer group than health control group（P〈0.01）,which was measured by ELISA.Apo-A1 could provide diagnostic utility to distinguish patients with bladder cancer from health controls at 19.21μg/L,with sensitivity and specificity of 88.3%and 83.7%.Moreover,the application of exfoliative urinary cytology in combination with the urine Apo-A1 detection could increase the sensitivity in detecting bladder cancer.Conclusion：Apo-A1 could be a potential biomarker for the diagnosis of bladder cancer.