Trevisani Francesco, Ghidini Michele, Larcher Alessandro, Lampis Andrea, Lote Hazel, Manunta Paolo, Alibrandi Maria Teresa Sciarrone, Zagato Laura, Citterio Lorena, Dell'Antonio Giacomo, Carenzi Cristina, Capasso Giovambattista, Rugge Massimo, Rigotti Paolo, Bertini Roberto, Cascione Luciano, Briganti Alberto, Salonia Andrea, Benigni Fabio, Braconi Chiara, Fassan Matteo, Hahne Jens Claus, Montorsi Francesco, Valeri Nicola
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Department of Urology, San Raffaele Scientific Institute, Milan, Italy.
Br J Cancer. 2016 Nov 22;115(11):1343-1350. doi: 10.1038/bjc.2016.329. Epub 2016 Nov 1.
A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes.
Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT-PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD.
The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy.
miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN.
相当一部分因透明细胞肾细胞癌（RCC）接受根治性肾切除术（RN）的患者在术后几年内会发展为慢性肾脏病（CKD）。慢性肾脏病对健康、社会和经济具有重要影响，目前尚无预测性生物标志物。微小RNA（miRs）是参与多种病理过程的小非编码RNA。
我们研究的主要目的是确定其失调可预测接受RN治疗患者发生CKD的miRs。使用nCounter NanoString技术对来自距离匹配的RCC大于3 cm的福尔马林固定石蜡包埋肾实质（皮质和髓质分别分离）的核糖核酸进行miR表达检测，共纳入71例连续接受RN治疗RCC的患者。通过逆转录聚合酶链反应（RT-PCR）和原位杂交进行验证。终点指标为术后12个月测量的RN后CKD。采用多变量逻辑回归和决策曲线分析来检验CKD预测指标的统计学和临床影响。
miR-193b-3p的过表达与接受RN治疗RCC的患者发生CKD的高风险相关，并成为CKD的独立预测指标。将miR-193b-3p添加到基于临床变量（包括性别和估计肾小球滤过率）的预测模型中，可使预测模型的敏感性从81%提高到88%。原位杂交显示，在无RN前肾病临床或生化证据的患者中，miR-193b-3p过表达与肾小管间质炎症和纤维化相关。
miR-193b-3p可能是一种有用的生物标志物，用于为RN后发生CKD高风险患者制定和实施监测策略。
