尿液EIF-5A2、AIB1检测在早期膀胱癌诊断和术后复发监测中的应用研究

We have reported that the up-regulation of EIF-5A2 and AIB1 gene expression was significantly associated with carcinogenesis and recurrence of bladder cancer, the average concentration of urinary EIF-5A2 and AIB1 protein of the patients with early stage bladder cancer were 4.0 and 2.9 times as the normal controls. Does the urinary detection of EIF-5A2 and AIB1 in diagnosing early stage bladder cancer outperform NMP22 and BTA test which are commonly used in clinical diagnosis? Firstly, we intend to use ELISA assay to detect the concentration of urinary EIF-5A2 and AIB1 protein with 300 cases early stage bladder cancer patients and normal controls, acquire the sensitivity and specificity through ROC curve, compare with NMP22 and BTA test, and evaluate the accuracy of uni- or multi-biomarker diagnosis.Secondly, the patients with early stage bladder cancer will be followed prospectively after surgery, the variety of the biomarkers concentration will be monitored during the follow-up, the accuracy of the biomarkers concentration and their velocity in diagnosing recurrence will be evaluated through ROC curve and time-concentration curve. This study can systematically assess the clinical value of urinary detection of EIF-5A2 and AIB1 in diagnosing early stage bladder cancer and monitoring recurrence, and comfirm whether the velocity of biomarkers concentration can be a new diagnostic method of the recurrence of bladder cancer.

我们报道了膀胱癌发生和复发时EIF-5A2、AIB1基因的表达显著上调,并发现早期膀胱癌患者尿EIF-5A2、AIB1蛋白平均浓度为正常人的4.0、2.9倍。那么,尿液EIF-5A2和AIB1检测诊断早期膀胱癌的准确度是否优于临床常用的NMP22和BTA？我们拟对300例早期膀胱癌患者和正常对照采用ELISA法检测尿液EIF-5A2和AIB1蛋白浓度,绘制ROC曲线,计算敏感度和特异度,与尿NMP22、BTA检测作比较,评估单一瘤标诊断及联合诊断的准确度；其次，对早期膀胱癌术后患者前瞻性随访,监测尿EIF-5A2、AIB1、NMP22和BTA浓度变化,分别绘制ROC曲线和时间浓度曲线,评估各瘤标静态浓度和动态浓度变化速度诊断肿瘤复发的准确度。本项目能系统评估尿EIF-5A2和AIB1检测在早期膀胱癌诊断和术后监测的应用价值,并确定尿液瘤标动态浓度变化速度能否成为监测膀胱癌术后复发的新方法。

我们发现EIF-5A2和AIB1基因在膀胱癌组织中的表达较癌旁正常膀胱粘膜有显著性上调，EIF-5A2和AIB1基因的过度表达与早期膀胱癌TURBt术后复发、进展存在显著的相关性。在体内外实验中敲除内源性AIB1表达能抑制膀胱癌细胞株的生长/增殖。我们完成了对膀胱癌患者及正常对照病例的尿液AIB1、EIF5A-2及NMP22尿液蛋白浓度的检测，并评价了各检测指标在膀胱癌早期诊断中的应用价值; 我们将AIB1、EIF5A-2及NMP22构建诊断模型，发现模型具有提高膀胱癌诊断准确度的优势。我们完成尿液EIF-5A2、AIB1检测在早期膀胱癌诊断中的应用研究之余，进一步对早期膀胱癌行TURBt术后患者进行跟踪随访，进行尿液EIF-5A2、AIB1检测在早期膀胱癌术后复发监测中的应用研究。目前该项目已发表sci相关论文11篇（均已标注），获得发明专利1项，这些成果为以后相关课题更深一步的进展提供了充足的理论依据以及奠定了基础。