Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

// Daniela Cabibi 1, * , Stefano Caruso 2, * , Viviana Bazan 2, * , Marta Castiglia 2 , Giuseppe Bronte 2 , Sabrina Ingrao 1 , Daniele Fanale 2 , Antonina Cangemi 2 , Valentina Calo 2 , Angela Listi 2 , Lorena Incorvaia 2 , Antonio Galvano 2 , Gianni Pantuso 3 , Eugenio Fiorentino 3 , Sergio Castorina 4, # , Antonio Russo 2, # 1 Department of Science for Promotion of Health and Mother and Child Care, Section of Human Pathology, University of Palermo, 90127 Palermo, Italy 2 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy 3 Department of Surgical, Oncological and Oral Sciences, Section of Surgical Oncology, University of Palermo, 90127 Palermo, Italy 4 Fondazione Mediterranea "G.B. Morgagni", Department of Biomedical and Biotechnological Sciences, University of Catania, 95100 Catania, Italy * These authors contributed equally to this work # Co-last authors, these authors contributed equally to this work Correspondence to: Antonio Russo, email: antonio.russo@usa.net Keywords: microRNA, Barrett’s esophagus, columnar-lined oesophagus, esophagitis, metaplasia Received: March 24, 2016      Accepted: May 05, 2016      Published: June 25, 2016 ABSTRACT Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett’s metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett’s esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined oesophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients.