Oncotarget

Research Papers:

Prognostic value of circulating microRNAs in upper tract urinary carcinoma

Ruth Montalbo, Laura Izquierdo, Mercedes Ingelmo-Torres, Juan José Lozano, David Capitán, Antonio Alcaraz and Lourdes Mengual _

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Oncotarget. 2018; 9:16691-16700. https://doi.org/10.18632/oncotarget.24672

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Abstract

Ruth Montalbo1,*, Laura Izquierdo1,*, Mercedes Ingelmo-Torres1, Juan José Lozano2, David Capitán1, Antonio Alcaraz1 and Lourdes Mengual1

1Department and Laboratory of Urology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain

2CIBERehd, Plataforma de Bioinformática, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas, Universidad de Barcelona, Barcelona, Spain

*These authors have contributed equally to this work

Correspondence to:

Lourdes Mengual, email: lmengual@clinic.cat

Keywords: biomarkers; microRNA; serum; tumour progression; upper urinary tract urothelial carcinoma

Received: November 22, 2017    Accepted: February 26, 2018    Published: March 30, 2018

ABSTRACT

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.


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