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dc.contributor.authorRickelt, Steffen
dc.contributor.authorNeyaz, Azfar
dc.contributor.authorCondon, Charlene
dc.contributor.authorWhittaker, Charles A
dc.contributor.authorZaidi, Ali H
dc.contributor.authorTaylor, Martin S
dc.contributor.authorAbbruzzese, Genevieve
dc.contributor.authorMattia, Anthony R
dc.contributor.authorZukerberg, Lawrence
dc.contributor.authorShroff, Stuti G
dc.contributor.authorYilmaz, Omer H
dc.contributor.authorYilmaz, Osman
dc.contributor.authorWu, Elizabeth Y
dc.contributor.authorChoi, Won-Tak
dc.contributor.authorJobe, Blair A
dc.contributor.authorOdze, Robert D
dc.contributor.authorPatil, Deepa T
dc.contributor.authorDeshpande, Vikram
dc.contributor.authorHynes, Richard O
dc.date.accessioned2022-12-09T17:43:10Z
dc.date.available2022-12-09T17:43:10Z
dc.date.issued2022
dc.identifier.urihttps://hdl.handle.net/1721.1/146811
dc.description.abstract<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Experimental Design:</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>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 &amp;lt; 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 &amp;lt; 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%.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>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.</jats:p> </jats:sec>en_US
dc.language.isoen
dc.publisherAmerican Association for Cancer Research (AACR)en_US
dc.relation.isversionof10.1158/1078-0432.CCR-21-2822en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleAgrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarkeren_US
dc.typeArticleen_US
dc.identifier.citationRickelt, Steffen, Neyaz, Azfar, Condon, Charlene, Whittaker, Charles A, Zaidi, Ali H et al. 2022. "Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker." Clinical Cancer Research, 28 (6).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.relation.journalClinical Cancer Researchen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2022-12-09T17:24:38Z
dspace.orderedauthorsRickelt, S; Neyaz, A; Condon, C; Whittaker, CA; Zaidi, AH; Taylor, MS; Abbruzzese, G; Mattia, AR; Zukerberg, L; Shroff, SG; Yilmaz, OH; Yilmaz, O; Wu, EY; Choi, W-T; Jobe, BA; Odze, RD; Patil, DT; Deshpande, V; Hynes, ROen_US
dspace.date.submission2022-12-09T17:24:41Z
mit.journal.volume28en_US
mit.journal.issue6en_US
mit.licenseOPEN_ACCESS_POLICY
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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