Authors: Pauline Bus Christine Kestens Fiebo Jan Willem Ten Kate Wilbert Peters Joost Paulus Hubertus Drenth Jeanine Merel Leonoor Roodhart Peter Derk Siersema Jantine Wilhelmina Paula Maria van Baal
Publish Date: 2015/11/19
Volume: 51, Issue: 6, Pages: 560-570
Abstract
Circulating microRNAs miRNAs have been suggested as novel markers for various diseases The goal of this pilot study was to identify circulating miRNAs differentially expressed comparing Barrett’s esophagus BE esophageal adenocarcinoma EAC and controlsMicroRNA expression profiling was performed by qPCR array using plasma from six controls and eight BE and eight EAC patients Validation was performed by analyzing the expression of six selected miRNAs by qRTPCR in 115 plasma samples of controls BE and EAC patients Diagnostic accuracy was evaluated by area under the curve AUC analysisWe identified three miRNAs that were elevated in EAC and four miRNAs that were elevated in BE Further validation showed that miRNA3825p was significantly increased and miRNA133a3p significantly decreased in EAC miRNA1945p and miRNA451a were significantly increased and miRNA1365p significantly decreased in BE versus controls A combination of three or more miRNAs was found to have a good diagnostic performance in discriminating BE from controls AUC 0832 EAC from controls AUC 0846 and BE from EAC AUC 0797Barrett’s esophagus BE is a premalignant condition of the distal esophagus characterized by the metaplastic replacement of normal stratified squamous epithelium by specialized intestinal columnar epithelium 1 BE is associated with an increased risk of progression to esophageal adenocarcinoma EAC with an estimated annual incidence of 033 2 During the last few decades incidence rates of BE and EAC have increased dramatically in the Western world 3The current approach of BE screening includes routine surveillance endoscopy with histopathological analysis of biopsies taken during endoscopy For the diagnosis of BE and EAC morphological assessment of biopsies is the golden standard The histological presence or absence of dysplasia is the basis for the advised endoscopic followup intervals in BE Unfortunately sampling bias occurs 4 and there is an ongoing discussion on whether BE surveillance is indeed costeffective 5 Additionally histological grading of BE biopsies is subject to considerable interobserver variability 6 7 Moreover in over 90 of new EAC cases BE was not diagnosed before 8 This suggests that it is important to have easytouse markers that are able to distinguish BE and EAC patients from the normal populationMicroRNAs miRNAs are small noncoding RNAs of approximately 21–25 nucleotides long They function by negatively influencing the protein translation machinery via translational repression or mRNA degradation 9 Expression profiles of miRNAs in various cancers have been investigated showing that miRNA expression profiles are disease and tissuespecific and therefore can be considered candidate biomarkers 10 11 12 13 In addition miRNA expression profiling of BE and EAC biopsies has shown tissuespecific miRNAs 14 15 16 17
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