Dynamic changes in microRNA expression profiles reflect progression of Barrett's esophagus to esophageal adenocarcinoma
Language English Country Great Britain, England Media print-electronic
Document type Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
25784377
DOI
10.1093/carcin/bgv023
PII: bgv023
Knihovny.cz E-resources
- MeSH
- Adenocarcinoma genetics pathology MeSH
- Barrett Esophagus genetics pathology MeSH
- Esophagus metabolism pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- MicroRNAs genetics MeSH
- Biomarkers, Tumor genetics MeSH
- Esophageal Neoplasms genetics pathology MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Disease Progression MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Retrospective Studies MeSH
- ROC Curve MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Gene Expression Profiling * MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- MicroRNAs MeSH
- Biomarkers, Tumor MeSH
Esophageal adenocarcinoma (EAC) is highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. MicroRNAs (miRNAs) are small, non-coding RNAs that function as posttranscriptional regulators of gene expression and were repeatedly proved to play key roles in pathogenesis of BE as well as EAC. In our study, we used Affymetrix GeneChip miRNA arrays to obtain miRNA expression profiles in total of 119 tissue samples [24 normal esophageal mucosa (EM), 60 BE and 35 EAC]. We identified a number of miRNAs, that showed altered expression progressively in sequence EM, BE and EAC, including for instance miR-21, miR-25, miR-194 and miR-196a with increasing levels (P < 0.0015) and miR-203, miR-205, miR-210 and miR-378 with decreasing levels (P < 0.0001). The subsequent analysis revealed four diagnostic miRNA signatures enabling to distinguish EM and BE [12 miRNAs, area under curve (AUC) = 0.971], EM and EAC (13 miRNAs, AUC = 1.0), BE without and BE with dysplasia (21 miRNAs, AUC = 0.856) and BE without dysplastic changes and BE with dysplasia together with EAC (2 miRNAs, AUC = 0.886). We suggest that miRNA expression profiling expands current knowledge in molecular pathology of Barrett's-based carcinogenesis and enables identification of molecular biomarkers for early detection of BE dysplasia and progression to EAC.
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