Vergho Daniel, Kneitz Susanne, Rosenwald Andreas, Scherer Charlotte, Spahn Martin, Burger Maximilian, Riedmiller Hubertus, Kneitz Burkhard
Department of Urology and Paediatric Urology, Julius-Maximilians-University Medical Centre of Würzburg, Würzburg, Germany.
BMC Cancer. 2014 Jan 15;14:25. doi: 10.1186/1471-2407-14-25.
Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs.
Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC).
RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease.
A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.
肾细胞癌（RCC）死亡率高。迄今为止，尚未建立针对早期阶段的基于临床或分子预后指标的可靠癌症特异性生存（CSS）风险分层。小非编码RNA基因产物（miRNA）的转录谱分析对于预后分层似乎很有前景。分析了一大群RCC患者中miR-21和miR-126的表达；基于这两种miRNA的表达水平构建了联合风险评分（CRS）模型。
通过qRT-PCR评估了n = 139例透明细胞RCC患者肿瘤及相邻非肿瘤组织中miR-21和miR-126的表达。评估了miR-21和miR-126表达与各种临床参数的关系。通过单因素和多因素COX回归分析参数。分别为两种miR确定由COX模型得出的z评分衍生的一个因子，并通过将miR-21和miR-126的相对表达乘以该因子来计算联合风险评分（CRS）。通过使用赤池信息准则（AIC）的相对拟合优度选择最佳拟合COX模型。
有和没有miR-21上调及miR-126下调的RCC在同步转移状态和CSS方面有显著差异。miR-21上调和miR-126下调具有独立的预后意义。基于两种miR表达的联合风险评分（CRS）在预测CSS方面显示出高敏感性和特异性，且预测独立于任何其他临床病理参数。CRS与CSS的关联在一个包含疾病进展高风险和低风险患者的测试队列中得到成功验证。
miR-21和miR-126的联合表达水平在两个独立的RCC队列中准确预测了CSS，并且在评估预后的临床应用中似乎是可行的。
