摘要目的 探讨胆管癌组织中支架蛋白4A(CUL4A)的表达及其临床意义.方法 收集山东省滨州市人民医院2011年2月至2013年12月的35例新鲜胆管癌和15例正常胆管手术切除标本,应用实时荧光定量PCR(qRT-PCR)技术检测CUL4A mRNA的表达.收集山东省滨州市人民医院2008年1月至2014年1月的72例胆管癌及36例正常胆管组织,应用免疫组织化学方法检测CUL4A的表达情况.分析CUL4A的表达与患者临床病理特征及预后的关系.结果 胆管癌组织中CUL4A mRNA表达明显高于正常胆管组织(3.876 ±0.975∶1.216 ±0.265),差异有统计学意义(t=12.23,P＜0.001).CUL4A在胆管癌组织和正常胆管组织中的阳性表达率分别为70.8％ (51/72)和2.8％ (1/36),差异有统计学意义(x2=44.524,P＜0.001).CUL4A在胆管癌中的表达与肿瘤分化程度(x2=4.341,P=0.037)、神经浸润(x2=8.326,P=0.004)、TNM分期(x2=7.745,P=0.005)、淋巴结转移(x2=3.869,P =0.049)及血管侵袭(x2=5.555,P=0.018)有关.生存分析结果显示,CUL4A阳性患者的中位生存时间显著短于阴性患者(32.40个月∶51.30个月),差异有统计学意义(x2=6.561,P=0.011).结论 胆管癌组织中CUL4A表达较正常胆管组织显著升高.CUL4A在肿瘤侵袭转移过程中发挥重要作用并提示不良预后,可能成为胆管癌诊断和治疗的一个新靶点.

abstractsObjective To explore the expression of cullin 4A (CUL4A) in cholangiocarcinoma tissues and its clinical significance.Methods Primary fresh cholangiocarcinoma tissues (n =35) and normal bile duct tissues (n =15) from patients who underwent curative surgery in Binzhou People's Hospital of Shandong Province from February 2011 to December 2013 were collected.The expressions of CUL4A mRNA were detected by quantitative real-time PCR (qRT-PCR).Then,cholangiocarcinoma tissues (n =72) and normal bile duct tissues (n =36) from patients who underwent curative surgery in Binzhou People's Hospital of Shandong Province from January 2008 to January 2014 were collected.The expressions of CUL4A protein were tested by immunohistochemistry.The relationships between the expression of CUL4A and the patients' clinicopathologic features and prognosis were analyzed.Results The expression of CUL4A mRNA in cholangiocarcinoma tissues was obviously higher than that in normal bile duct tissues (3.876 ±0.975 vs.1.216 ±0.265),and the difference was statistically significant (t =12.23,P ＜ 0.001).The positive rates of CUL4A protein in cholangiocarcinoma and normal bile duct tissues were 70.8％ (51/72) and 2.8％ (1/36) respectively,and the difference was statistically significant (x2 =44.524,P ＜ 0.001).The expression of CUL4A protein in cholangiocarcinoma was related to the differentiated degree (x2 =4.341,P =0.037),neural invasion (x2 =8.326,P =0.004),TNM stage (x2 =7.745,P =0.005),lymph node metastasis (x2 =3.869,P =0.049) and vascular invasion (x2 =5.555,P =0.018).Survival analysis results showed that the median survival time of CUL4A positive patients was significantly shorter than that of CUL4A negative patients (32.40 months vs.51.30 months),and the difference was statistically significant (x2 =6.561,P =0.011).Conclusion The expression of CUL4A in cholangiocarcinoma tissues is higher than that in normal bile tissues.CUL4A plays an important role in the process of tumor invasion and metastasis and indicates poor prognosis,which may become a potential target for the diagnosis and therapy of the cholangiocarcinoma.