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

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.

Circulating microRNAs as potential biomarkers to detect transformation of Barrett’s oesophagus to oesophageal adenocarcinoma

“… 49–51 Of note, circulating levels of group 2 miRNAs were elevated during the development of BO compared with those in healthy controls ( figure 3B ). Cabibi et al 52 also reported that tissue and circulating miR-143-3 p levels are elevated during metaplastic transformation of the oesophagus, suggesting that group 2 miRNA may be associated with intestinal differentiation.…”

Bioinformatic analyses of microRNA-targeted genes and microarray-identified genes correlated with Barrett's esophagus

“…Luzna P et al [13] proposed that miR-192 and miR-196a were up-regulated with an increase during BE progression. Cabibi D et al [17] found increased expression levels of miR-143, miR-145, miR-194 and miR-215 in BE, while miR-203 and miR-205 were down-regulated. Wijnhoven B P et al [19].…”

“…Endogenous miRNAs interact with the 3'-UTR of target mRNA to suppress post-transcription of genes [5,6]. Previous studies have underscored the relevance of miRNAs as potential biomarkers for disease diagnosis, cancer prediction and prognosis assessment, including BE and EAC [10,11,13,15,[17][18][19][20]22,[29][30][31][32][33]. These studies mostly focused on BE carcinogenesis and were less concerned with its pathogenesis.…”

“…Microarrays have been widely used to explore expression genes, including miRNAs expression profiling. A series of studies [11,[13][14][15][16][17] have indicated that microarrays provide a more effective means of identifying and verifying potential biomarkers in BE at the molecular level.…”

Identification of key pathways and genes in Barrett's esophagus using integrated bioinformatics methods

“…miRNAs are a group of endogenous non-coding RNA molecules that act as negative regulators in post-transcriptional gene regulation. Recent studies reported that aberrant miRNA expression is associated with the development of BE ( 30 , 31 ). The current study found five differentially expressed miRNAs, including two upregulated DEmiRNAs and three downregulated DEmiRNAs.…”