膀胱癌中DR4和DR5的表达水平与患者术后化疗及患者预后的关系

Expression of DR4,and DR5 in Bladder Cancer:Correlation With Response to Adjuvant Therapy and Implications of Prognosis

目的在临床前期实验中,肿瘤坏死因子相关凋亡诱导配体(TRAIL)与化疗药物在抗癌中存在协同作用。表阿霉素广泛应用于膀胱癌的辅助化疗中。在这里,我们假设膀胱癌中死亡受体DR4和DR5表达水平与膀胱癌患者的术后化疗及预后相关。方法采用免疫组化法检测229例经尿道切除术后的膀胱癌患者及癌旁正常组织中的DR4和DR5的表达。结果膀胱癌患者细胞质中DR4和DR5的表达率分别为75.1%和74.2%。DR4与DR5均高表达的患者术后10年随访期间的无复发生存率明显好于低表达者。多变量分析显示DR4(P<0.001)、DR5(P<0.001)的表达及表阿霉素的治疗(P=0.034)是膀胱癌患者预后的独立指标,而且表阿霉素治疗能够明显提高DR4(P=0.006)或DR5(P=0.042)高表达的膀胱癌患者的无复发生存率。结论 DR4和DR5均高表达的患者可能更适合接受表阿霉素治疗。

Objective To explore the interrelationship of death receptors DR4 and DR5 expressions level with pa-tient prognosis and the response to adj uvant therapy in bladder cancer.Methods The expression of DR4 and DR5 was studied using immunohistochemistry of paraffin-embedded tumor specimens from 229 bladder cancer patients who had undergone transurethral resection.Results Cytoplasmic DR4,and DR5 expressions were detected in 75.1%,and 74.2% of bladder cancer patients,respectively.Patients with bladder cancer with either high DR4 or DR5 expression had a significantly longer postoperative recurrence-free rate than those with low expression of both during the 10-year follow-up.Multivariate analysis revealed that the expression of DR4 （P〈.001）,DR5（P〈.001）and epirubicin therapy（P=.034）were independent prognostic indicators of bladder cancer.Furthermore,epirubicin therapy significantly improved recur-rence-free rate for the patients with DR4-high（P=.006）or DR5-high（P=.042）tumor.Conclusion Patients with high ex-pression of both DR4 and DR5 might benefit from epirubicin therapy.