miRNAs in the metaplastic transformation of the esophagus: something in the way toward carcinogenesis.

Background: Barrett's esophagus (BE) is a precancerous lesion that predisposes to development of esophageal adenocarcinoma (EAC) and it is associated with gastroesophageal reflux disease. Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett’s metaplasia and adenocarcinoma are almost unknown and there is an increasing interest in the developing of more objective biomarkers that can improve risk prediction. Several evidences suggest that some miRNAs are differentially expressed in the BE and EAC. Among them, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in the metaplasia and in neoplastic progression. Aim: The aim of this study was to analyze deregulated miRNAs in the serum and in esophageal mucosal tissue biopsies from subjects undergoing upper gastrointestinal endoscopy in order to better understand the role that these could have in the pathogenesis of the esophageal metaplasia and to identify some biomarkers that could be associated with different stages of esophageal disease. Materials and methods: Esophageal mucosal fresh tissue biopsies and blood samples were collected. Simultaneously other biopsies were sent to Human Pathology and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 expression levels in 60 disease/normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined oesophagus (CLO) or BE. Simultaneously, the serum levels of these miRNAs were assessed. MiRNA expression was normalized to RNU48. Changes in miRNA expression levels were determined using a comparative CT method. Results: Endoscopic evidence of BE was confirmed by paired-histological analysis. 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 significantly lower in BE tissues compared with their corresponding normal tissues. In addition, the analysis of esophageal mucosa of patients with CLO and esophagitis showed that these miRNAs were deregulated similarly but to a lesser extent keeping the same trend. Analysis on the circulating microRNA levels showed that only miR-215 was significantly upregulated in the Barrett group compared to Esophagitis. Conclusions: Elevated miR-143, miR-145, miR-194, miR-215 and reduce miR-203, miR-205 expression levels was observed in esophageal mucosa with subjects with BE. Interestingly, the same trend was found to a lesser degree in individuals with CLO and esophagitis and CLO appeared unequivocally as intermediate step between Esophagitis and BE. In addition, serum miR-215 could be a potential non-invasive biomarker for Barrett's esophagus. These findings suggest that these miRNAs may be involved in the neoplastic/metaplastic progression. miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients.