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Data from Agrin Loss in Barrett's Esophagus-Related Neoplasia and Its Utility as a Diagnostic and Predictive Biomarker

Authors :
Richard O. Hynes
Vikram Deshpande
Deepa T. Patil
Robert D. Odze
Blair A. Jobe
Won-Tak Choi
Elizabeth Y. Wu
Osman Yilmaz
Omer H. Yilmaz
Stuti G. Shroff
Lawrence Zukerberg
Anthony R. Mattia
Genevieve Abbruzzese
Martin S. Taylor
Ali H. Zaidi
Charles A. Whittaker
Charlene Condon
Azfar Neyaz
Steffen Rickelt
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

Abstract

Purpose: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.Experimental Design: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.Results: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%.Conclusions: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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....5f6d5087fd8ddc60f102d9923f7581f9
Full Text :
https://doi.org/10.1158/1078-0432.c.6531101.v1