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. 2018 Mar 30;9(24):16691-16700.
doi: 10.18632/oncotarget.24672.

Prognostic value of circulating microRNAs in upper tract urinary carcinoma

Ruth Montalbo #  1 , Laura Izquierdo #  1 , Mercedes Ingelmo-Torres  1 , Juan José Lozano  2 , David Capitán  1 , Antonio Alcaraz  1 , Lourdes Mengual  1
Affiliations

Prognostic value of circulating microRNAs in upper tract urinary carcinoma

Ruth Montalbo et al. Oncotarget. .

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.

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

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Heat map showing the 38 miRNAs differentially expressed between patients with progressing and non-progressing UTUC (N=12)
Red pixels correspond to a greater abundance of miRNA in the serum samples, whereas green pixels indicate lower miRNA levels. Rows represent individual miRNAs and columns represent experimental samples.
Figure 2
Figure 2
Kaplan Meier curves for (A) tumour progression and (B) cancer-specific survival according to miR-151b expression values (N=33). Green line represents patients at low risk (expression cutoff≥4.21) and blue line represents patients at high risk (expression cutoff<4.21).
Figure 3
Figure 3. Network Analyst-derived protein–protein interactions network results
Network constructed with the 53 genes shared across most of data sets as seed proteins. Red nodes are most important interactions, followed by pink nodes and finally purple nodes. Nodes in blue represent those proteins interacting in Cancer pathways.
See this image and copyright information in PMC

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