title: Dynamic changes in microRNA expression profiles reflect progression of Barrett's esophagus to esophageal adenocarcinoma.
abstract: 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.
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, 656 53 Brno, Czech Republic, Central European Institute of Technology, Molecular Oncology II, Masaryk University, 625 00 Brno, Czech Republic, on.slaby@gmail.com.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, 779 00 Olomouc, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Srovnal
authors.affiliation: Central European Institute of Technology, Molecular Oncology II, Masaryk University, 625 00 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Radova
authors.affiliation: Department of Internal Medicine II - Gastroenterology and Hepatology, University Hospital, 779 00 Olomouc, Czech Republic and.
authors.forename: Jan
authors.initials: J
authors.lastname: Gregar
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, 656 53 Brno, Czech Republic, Central European Institute of Technology, Molecular Oncology II, Masaryk University, 625 00 Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Juracek
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Luzna
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, 656 53 Brno, Czech Republic, Central European Institute of Technology, Molecular Oncology II, Masaryk University, 625 00 Brno, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, 779 00 Olomouc, Czech Republic.
authors.forename: Marian
authors.initials: M
authors.lastname: Hajduch
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Ehrmann
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs