Predictive value of MicroRNAs in the progression of barrett esophagus to adenocarcinoma in a long-term follow-up study.
OBJECTIVE
The aim of this study is to identify a set of microRNAs (miRNAs) as prognostic molecular biomarkers for the progression of Barrett esophagus (BE) to esophageal adenocarcinoma (EAC) to rationalize the surveillance programs in patients with BE.


BACKGROUND
Histological dysplasia is currently used as the main biomarker to identify the BE patients at high risk for developing EAC. Although miRNA expression profiles in BE and EAC have been reported, it has not been established which set of miRNAs could constitute a robust diagnostic test to predict the progression of BE to EAC.


METHODS
miRNAs associated with progression of BE to EAC were identified using miRNA sequencing analysis. Further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in 2 groups of BE patients who either developed or did not develop adenocarcinoma after at least 5 years of follow-up.


RESULTS
Twenty-three miRNAs were identified by miRNA sequencing analysis in the carcinogenesis process associated with BE. qRT-PCR analysis using independent tissue samples confirmed differential expression for 19 of them (miR-let-7c, 7, 146a, 149, 153, 192, 192*, 194, 194*, 196a, 196b, 200a, 203, 205, 215, 424, 625, 625*, and 944). However, only miR-192, 194, 196a, and 196b showed a significantly higher expression in BE samples from patients with progression to EAC compared with those who did not progress to EAC.


CONCLUSIONS
These findings suggest that the expression pattern of a modest number of miRNAs in metaplasia biopsies could identify the BE patients at high risk for developing EAC. Therefore, it has potential use for the control and treatment of this malignancy.
Department of Surgery, University Hospital Virgen de la Arrixaca, Murcia, Spain.
Beatriz
B
Revilla-Nuin
Pascual
P
Parrilla
Juan Jose
JJ
Lozano
Luisa F Martínez
LF
de Haro
Angeles
A
Ortiz
Carlos
C
Martínez
Vicente
V
Munitiz
David Ruiz
DR
de Angulo
Juan
J
Bermejo
Joaquin
J
Molina
María L
ML
Cayuela
José
J
Yélamos
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019295:Computational Biology; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016015:Logistic Models; D035683:MicroRNAs / Q000378:metabolism*; D015999:Multivariate Analysis; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D059467:Transcriptome
D014408:Biomarkers, Tumor; D035683:MicroRNAs