Prediction of cancer progression in Barrett’s esophagus patients using miRNA profiling
2014
Background: Barrett’s esophagus (BE) is a metaplastic disease with risk to develop esophageal adenocarcinoma (EAC). Current screening method for BE patients (endoscopy and biopsy) is discomfort, expensive and relatively risky for patients. Moreover, the procedure is complicated by subjective histopathological examination. Approximately only 2% of BE patients annually progress to adenocarcinoma. The aim of our study was to identify miRNA profiles in order to predict cancer progression in high-risk BE patients. Methods and patients: FFPE samples were obtained from 68 patients (10 EAC, 4 high-grade and 21 low-grade dysplasia of esophagus, and 33 BE). There were 49 males and 19 females; median age was 58 years, range 27 - 97 years. Total RNA was purified from FFPE biopsy samples using Proteinase K treatment followed by RNeasy kit (Qiagen). Microarray analysis was performed using the GeneChip miRNA 3.0 Array (Affymetrix). The data were analyzed using “R” software and the Bioconductor package. Results: In total, 68 GeneChip miRNA 3.0 Arrays were performed in 68 patients (8 poor quality arrays were excluded). Expression profiles of 1733 human miRNAs, 1658 human pre-miRNAs and 2216 human sno-RNAs and sca-RNAs were analyzed. In supervised clustering analysis we found 29 differentially expressed miRNAs, 7 pre-miRNAs and 9 sno-RNAs (p 2) in EAC patients compared to BE patients. One of the dominant findings was decreased expression of miR-22 in EAC samples, which is known to function as a tumor suppressor and histone deacetylase 4 regulator. Conclusion: We have identified miRNA profiles allowing for better diagnostics of cancer progression in BE patients, which, however, will require further validation.
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