Agrin Loss in Barrett's Esophagus-Related Neoplasia and Its Utility as a Diagnostic and Predictive Biomarker.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 03 2022
15 03 2022
Historique:
received:
03
08
2021
revised:
29
09
2021
accepted:
10
11
2021
pubmed:
18
11
2021
medline:
16
4
2022
entrez:
17
11
2021
Statut:
ppublish
Résumé
There is an unmet need for identifying novel biomarkers in Barrett's esophagus that could stratify patients with regards to neoplastic progression. We investigate the expression patterns of extracellular matrix (ECM) molecules in Barrett's esophagus and Barrett's esophagus-related neoplasia, and assess their value as biomarkers for the diagnosis of Barrett's esophagus-related neoplasia and to predict neoplastic progression. Gene-expression analyses of ECM matrisome gene sets were performed using publicly available data on human Barrett's esophagus, Barrett's esophagus-related dysplasia, esophageal adenocarcinoma (ADCA) and normal esophagus. Immunohistochemical expression of basement membrane (BM) marker agrin (AGRN) and p53 was analyzed in biopsies of Barrett's esophagus-related neoplasia from 321 patients in three independent cohorts. Differential gene-expression analysis revealed significant enrichment of ECM matrisome gene sets in dysplastic Barrett's esophagus and ADCA compared with controls. Loss of BM AGRN expression was observed in both Barrett's esophagus-related dysplasia and ADCA. The mean AGRN loss in Barrett's esophagus glands was significantly higher in Barrett's esophagus-related dysplasia and ADCA compared with non-dysplastic Barrett's esophagus (NDBE; P < 0.001; specificity = 82.2% and sensitivity = 96.4%). Loss of AGRN was significantly higher in NDBE samples from progressors compared with non-progressors (P < 0.001) and identified patients who progressed to advanced neoplasia with a specificity of 80.2% and sensitivity of 54.8%. Moreover, the combination of AGRN loss and abnormal p53 staining identified progression to Barrett's esophagus-related advanced neoplasia with a specificity and sensitivity of 86.5% and 58.7%. We highlight ECM changes during Barrett's esophagus progression to neoplasia. BM AGRN loss is a novel diagnostic biomarker that can identify patients with NDBE at increased risk of developing advanced neoplasia.
Identifiants
pubmed: 34785582
pii: 1078-0432.CCR-21-2822
doi: 10.1158/1078-0432.CCR-21-2822
pmc: PMC8923984
mid: NIHMS1758218
doi:
Substances chimiques
Agrin
0
Biomarkers
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1167-1179Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : RI2408/1-1
Organisme : NIDDK NIH HHS
ID : K08 DK129824
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NIH HHS
ID : T32CA009216
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA163109
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009216
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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