Tang Kun, Xu Hua
1] Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [2] Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Sci Rep. 2015 May 14;5:10272. doi: 10.1038/srep10272.
To identify a robust panel of microRNA (miRNA) signatures that can distinguish renal cell carcinoma (RCC) from normal kidney using miRNA expression levels. We performed a comprehensive meta-analysis of 29 published studies that compared the miRNA expression profiles of RCC tissues and adjacent normal tissues (NT) to determine candidate miRNAs as prognostic biomarkers for RCC. Using vote-counting strategy and robust rank aggregation method, we identified a statistically significant miRNA meta-signature of two upregulated (miR-21, miR-210) and three downregulated (miR-141, miR-200c and miR-429) miRNAs. X-tile plot was used to generate the optimum cut-off point for the 15 different deregulated miRNAs and Kaplan-Meier method was used to calculate CSS. In a cohort of 45 patients, the high expression of miR-21 (HR: 5.46, 95%CI: 2.02-53.39) and miR-210 (HR: 6.85, 95%CI: 2.13-43.36), the low expression of miR-141 (HR: 0.16, 95%CI: 0.004-0.18), miR-200c (HR: 0.08, 95%CI: 0.01-0.43) and miR-429 (HR: 0.18, 95%CI: 0.02-0.50) were associated with poor cancer-specific survival (CSS) following RCC resection. We also constructed a five-miRNAs-based classifier as a reliable prognostic and predictive tool for CSS in patients with RCC, especially in clear cell RCC (ccRCC) (HR: 5.46, 95% CI: 1.51-19.66). This method might facilitate patient counselling and individualise management of RCC.
利用微小RNA（miRNA）表达水平，确定一组能区分肾细胞癌（RCC）与正常肾组织的强大miRNA特征。我们对29项已发表研究进行了全面的荟萃分析，这些研究比较了RCC组织和相邻正常组织（NT）的miRNA表达谱，以确定作为RCC预后生物标志物的候选miRNA。采用投票计数策略和稳健秩聚合方法，我们确定了一个具有统计学意义的miRNA元特征，包括两个上调的（miR-21、miR-210）和三个下调的（miR-141、miR-200c和miR-429）miRNA。使用X-tile图生成15种不同失调miRNA的最佳截断点，并使用Kaplan-Meier方法计算癌症特异性生存率（CSS）。在一组45例患者中，miR-21（HR：5.46，95%CI：2.02-53.39）和miR-210（HR：6.85，95%CI：2.13-43.36）的高表达，miR-141（HR：0.16，95%CI：0.004-0.18）、miR-200c（HR：0.08，95%CI：0.01-0.43）和miR-429（HR：0.18，95%CI：0.02-0.50）的低表达与RCC切除术后不良的癌症特异性生存率（CSS）相关。我们还构建了一个基于5种miRNA的分类器，作为RCC患者CSS的可靠预后和预测工具，尤其是在透明细胞RCC（ccRCC）中（HR：5.46，95%CI：1.51-19.66）。该方法可能有助于患者咨询和RCC的个体化管理。
