Circulating microRNA expression profiling revealed miR-92a-3p as a novel biomarker of Barrett's carcinogenesis.
Barrett’s esophagus
Expression signature
Liquid biopsy
Metaplasia
miRNA
Journal
Pathology, research and practice
ISSN: 1618-0631
Titre abrégé: Pathol Res Pract
Pays: Germany
ID NLM: 7806109
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
09
01
2020
revised:
24
02
2020
accepted:
27
02
2020
pubmed:
7
3
2020
medline:
27
2
2021
entrez:
6
3
2020
Statut:
ppublish
Résumé
The main intent of secondary prevention strategies for Barrett's esophagus (BE) patients relies in the prompt identification of patients with dysplasia (or intra-epithelial neoplasia; IEN) and early-stage adenocarcinoma (Barrett's adenocarcinoma; BAc). Despite the adequate characterization of the molecular landscape characterizing Barrett's carcinogenesis, no tissue and/or circulating biomarker has been approved for clinical use. A series of 25 serum samples (12 BE, 5 HG-IEN and 8 BAc) were analyzed for comprehensive miRNA profiling and ten miRNAs were found to be significantly dysregulated. In particular seven were upregulated (i.e. miR-92a-3p, miR-151a-5p, miR-362-3p, miR-345-3p, miR-619-3p, miR-1260b, and miR-1276) and three downregulated (i.e. miR-381-3p, miR-502-3p, and miR-3615) in HG-IEN/BAc samples in comparison to non-dysplastic BE. All the identified miRNAs showed significant ROC curves in discriminating among groups with AUC values range of 0.75-0.83. Validation of the results were performed by droplet digital PCR in two out of three tested miRNAs. To understand the cellular source of circulating miR-92a-3p, we analyzed its expression in endoscopy biopsy samples by both qRT-PCR and ISH analyses. As observed in serum samples, miR-92a-3p was over-expressed in HG-IEN/BAc samples in comparison to naïve esophageal squamous mucosa and BE and was mainly localized within the epithelial cells, supporting neoplastic cells as the main source of the circulating miRNA. Our data further demonstrated that circulating miRNAs are a promising mini-invasive diagnostic tool in the secondary follow-up and management of BE patients. Larger multi-Institutional studies should validate and investigate the most adequate miRNAs profile in discriminating BE patients in specific risk classes.
Identifiants
pubmed: 32131978
pii: S0344-0338(20)30076-5
doi: 10.1016/j.prp.2020.152907
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Circulating MicroRNA
0
MIRN92 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
152907Informations de copyright
Copyright © 2020 Elsevier GmbH. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The other authors have no competing interests to declare related to the presented data.