Montalbo Ruth, Izquierdo Laura, Ingelmo-Torres Mercedes, Lozano Juan José, Capitán David, Alcaraz Antonio, Mengual Lourdes
Department and Laboratory of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.
CIBERehd, Plataforma de Bioinformática, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas, Universidad de Barcelona, Barcelona, Spain.
Oncotarget. 2018 Mar 30;9(24):16691-16700. doi: 10.18632/oncotarget.24672.
The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC.
迫切需要鉴定上尿路尿路上皮癌（UTUC）的预后生物标志物以预测肿瘤进展。本研究旨在鉴定血清微小RNA（miRNA），其可能作为UTUC患者肿瘤进展和生存的微创预测生物标志物。为此，前瞻性纳入了33例在巴塞罗那医院诊所接受根治性肾输尿管切除术的UTUC患者。使用nCounter® miRNA表达分析评估这些患者血清样本中800种miRNA的表达。该研究分为初始发现阶段（n = 12）和验证阶段（n = 21）。采用Cox回归分析进行生存分析。该系列的中位随访时间（范围）为42个月（9 - 100个月）。在发现阶段，在进展期和非进展期UTUC患者之间鉴定出38种差异表达的miRNA（p < 0.05）。在另一组独立的UTUC患者中对这38种miRNA进行验证，证实其中18种存在差异表达（p < 0.05）。Cox回归分析显示，miR - 151b和病理分期是肿瘤进展（HR = 0.33，p < 0.001和HR = 2.62，p = 0.006）以及癌症特异性生存（HR = 0.25，p < 0.001和HR = 3.98，p = 0.003）的显著预后因素。生存曲线显示，miR - 151b能够区分两组UTUC患者，其肿瘤进展概率（p = 0.006）和癌症特异性生存概率（p = 0.034）存在高度显著差异。尽管这些数据需要外部验证，但血清中的miRNA分析似乎是UTUC患者有价值的预后工具。特别是，血清中miR - 151b的差异表达可能作为UTUC的微创预后工具。
