MicroRNA Profiling in Patients with Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy.

Katerina Popovska-Jankovic,Rade Cukuranovic,Ljubinka Jankovic-Velickovic,Draga Toncheva,Vladisav Stefanovic,Momir Polenakovic,Slavica Stojnev,Predrag Noveski,Rada Staneva,Dijana Plaseska-Karanfilska

doi:10.1155/2016/7450461

Abstract

Balkan endemic nephropathy (BEN) is a disease that affects people that live in the alluvial plains along the tributaries of the Danube River in the Balkan region. BEN is a chronic tubulointerstitial disease with a slow progression to terminal renal failure and has strong association with upper tract urothelial carcinoma (UTUC). There are several hypotheses about the etiology of BEN, but only the toxic effect of aristolochic acid has been confirmed as a risk factor in the occurrence of the disease. Aberrantly expressed miRNAs have been shown to be associated with many types of cancers. A number of studies have investigated the expression of microRNAs in urothelial carcinoma, mainly on urothelial bladder cancer, and only a few have included patients with UTUC. Here we present the first study of microRNA profiling in UTUC tissues from patients with BEN (BEN-UTUC) and patients with UTUC from nonendemic Balkan regions (non-BEN-UTUC) in comparison to normal kidney tissues. We found 10 miRNAs that were differentially expressed in patients with BEN-UTUC and 15 miRNAs in patients with non-BEN-UTUC. miRNA signature determined in BEN-UTUC patients differs from the non-BEN-UTUC patients; only miR-205-5p was mutual in both groups.

Highlights

Balkan endemic nephropathy (BEN) is a disease that affects people that live in the alluvial plains along the tributaries of the Danube River such as Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia
Preliminary qPCR analysis with RNU 44 control microRNA revealed that 15 RNA samples were with satisfactory quality for microRNA microarray analysis, including 7 samples with BEN-upper tract urothelial carcinoma (UTUC), 4 non-BEN-UTUC samples, and 4 nontumor samples
Statistical analysis using R Bioconductor and GeneSpring v12.5 software revealed a number of differentially expressed miRNAs (P < 0.05) and at least two log fold changes when BEN-UTUC and non-BEN-UTUC were compared to the normal kidney samples (Figure 1)

Summary

Introduction

Balkan endemic nephropathy (BEN) is a disease that affects people that live in the alluvial plains along the tributaries of the Danube River such as Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN is a chronic tubulointerstitial disease with a slow progression to terminal renal failure and has strong association with upper tract urothelial carcinoma (UTUC) [1,2,3,4,5,6]. In areas where BEN is endemic, the incidence of UTUC is significantly higher, even 100 times, than in nonendemic regions [3,4,5,6,7]. There are several hypotheses about the etiology of BEN: environmental factors (nephrotoxic agents that include lead intoxication, metal and metalloids, chronic intoxication with Aristolochia clematitis, ochratoxin A and Pliocene lignite, and viruses), genetic predisposition (genetic polymorphisms and immunological changes), and epigenetic mechanisms (DNA methylation and specific histone acetylation). The toxic effect of aristolochic acid, a nephrotoxic and carcinogenic plant alkaloid derived from Aristolochia clematitis, has already been confirmed as a factor in the occurrence of the disease [5, 9]

Methods

Results

Conclusion