Lei Ye, Li Zengbo, Qi Lin, Tong Shiyu, Li Bin, He Wei, Chen Minfeng
1 Department of Urology, Xiangya Hospital, Central South University , Changsha, China .
2 Department of General Surgery, Xiangya Hospital, Central South University , Changsha, China .
J Endourol. 2015 Nov;29(11):1302-8. doi: 10.1089/end.2015.0420. Epub 2015 Jul 23.
Upper urinary-tract urothelial carcinomas (UTUC) constitute 5% of urothelial malignancies. Prognostic biomarkers would allow lower risk surgical approaches for less aggressive UTUCs. One biomarker-Ki-67/mindbomb E3 ubiquitin protein ligase 1 (Ki-67/MIB-1)-shows promise in UTUC, but there have been conflicting findings regarding its prognostic role. The systematic review and meta-analysis aim to determine the prognostic value of Ki-67/MIB-1 in UTUC in terms of UTUC-specific mortality rate, 5-year disease-free survival, and 5-year overall survival (including disease-specific survival).
A systematic review of the current literature produced 654 records. A total of 13 studies consisting of 1030 patients were finally included in the meta-analysis. Hazard ratios (HRs) with 95% confidence intervals (CI) were extracted or estimated. The individual HR estimates were combined into a pooled HR using a fixed-effects model that summed homogeneity of the individual true HRs.
Patients with Ki-67/MIB-1 overexpression displayed significantly higher UTUC-specific mortality rate (pooled HR: 2.14, 95% CI: 1.73-2.64; p<0.00001), significantly reduced 5-year disease-free survival (pooled HR: 2.27, 95% CI: 1.79-2.92; p<0.00001), and significantly reduced 5-year overall survival (pooled HR=1.77; 95% CI: 1.39-2.23 p<0.00001). There was significant heterogeneity detected in the UTUC-specific mortality rate meta-analysis (I(2)=63%) and the 5-year disease-free survival meta-analysis (I(2)=65%), but there was no significant heterogeneity detected in the 5-year overall survival meta-analysis (I(2)=0%). Egger's testing showed that none of the outcomes were influenced by publication bias (p>0.05).
Ki-67/MIB-1 overexpression shows promise as a prognostic biomarker for UTUC patients and requires further investigation.
上尿路尿路上皮癌（UTUC）占尿路上皮恶性肿瘤的5%。预后生物标志物将有助于对侵袭性较小的UTUC采用风险较低的手术方法。一种生物标志物——Ki-67/ mindbomb E3泛素蛋白连接酶1（Ki-67/MIB-1）——在UTUC中显示出前景，但关于其预后作用的研究结果存在冲突。本系统评价和荟萃分析旨在根据UTUC特异性死亡率、5年无病生存率和5年总生存率（包括疾病特异性生存率）确定Ki-67/MIB-1在UTUC中的预后价值。
对当前文献进行系统评价得出654条记录。最终共有13项研究（包括1030例患者）纳入荟萃分析。提取或估计具有95%置信区间（CI）的风险比（HRs）。使用固定效应模型将个体HR估计值合并为汇总HR，该模型汇总了个体真实HR的同质性。
Ki-67/MIB-1过表达的患者显示出显著更高的UTUC特异性死亡率（汇总HR：2.14，95%CI：1.73-2.64；p<0.00001）、显著降低的5年无病生存率（汇总HR：2.27，95%CI：1.79-2.92；p<0.00001）以及显著降低的5年总生存率（汇总HR=1.77；95%CI：1.39-2.23，p<0.00001）。在UTUC特异性死亡率荟萃分析（I²=63%）和5年无病生存率荟萃分析（I²=65%）中检测到显著异质性，但在5年总生存率荟萃分析中未检测到显著异质性（I²=0%）。Egger检验表明，所有结果均未受发表偏倚影响（p>0.05）。
Ki-67/MIB-1过表达有望作为UTUC患者的预后生物标志物，需要进一步研究。
