Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker
<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 regar...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
American Association for Cancer Research (AACR)
2022
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| Online Access: | https://hdl.handle.net/1721.1/146811 |
| _version_ | 1810980818857754624 |
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| author | Rickelt, Steffen Neyaz, Azfar Condon, Charlene Whittaker, Charles A Zaidi, Ali H Taylor, Martin S Abbruzzese, Genevieve Mattia, Anthony R Zukerberg, Lawrence Shroff, Stuti G Yilmaz, Omer H Yilmaz, Osman Wu, Elizabeth Y Choi, Won-Tak Jobe, Blair A Odze, Robert D Patil, Deepa T Deshpande, Vikram Hynes, Richard O |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Rickelt, Steffen Neyaz, Azfar Condon, Charlene Whittaker, Charles A Zaidi, Ali H Taylor, Martin S Abbruzzese, Genevieve Mattia, Anthony R Zukerberg, Lawrence Shroff, Stuti G Yilmaz, Omer H Yilmaz, Osman Wu, Elizabeth Y Choi, Won-Tak Jobe, Blair A Odze, Robert D Patil, Deepa T Deshpande, Vikram Hynes, Richard O |
| author_sort | Rickelt, Steffen |
| collection | MIT |
| description | <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 &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 &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> |
| first_indexed | 2024-09-23T10:04:54Z |
| format | Article |
| id | mit-1721.1/146811 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:04:54Z |
| publishDate | 2022 |
| publisher | American Association for Cancer Research (AACR) |
| record_format | dspace |
| spelling | mit-1721.1/1468112022-12-10T03:36:07Z Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker Rickelt, Steffen Neyaz, Azfar Condon, Charlene Whittaker, Charles A Zaidi, Ali H Taylor, Martin S Abbruzzese, Genevieve Mattia, Anthony R Zukerberg, Lawrence Shroff, Stuti G Yilmaz, Omer H Yilmaz, Osman Wu, Elizabeth Y Choi, Won-Tak Jobe, Blair A Odze, Robert D Patil, Deepa T Deshpande, Vikram Hynes, Richard O Massachusetts Institute of Technology. Department of Biology <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 &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 &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> 2022-12-09T17:43:10Z 2022-12-09T17:43:10Z 2022 2022-12-09T17:24:38Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146811 Rickelt, 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). en 10.1158/1078-0432.CCR-21-2822 Clinical Cancer Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research (AACR) PMC |
| spellingShingle | Rickelt, Steffen Neyaz, Azfar Condon, Charlene Whittaker, Charles A Zaidi, Ali H Taylor, Martin S Abbruzzese, Genevieve Mattia, Anthony R Zukerberg, Lawrence Shroff, Stuti G Yilmaz, Omer H Yilmaz, Osman Wu, Elizabeth Y Choi, Won-Tak Jobe, Blair A Odze, Robert D Patil, Deepa T Deshpande, Vikram Hynes, Richard O Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker |
| title | Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker |
| title_full | Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker |
| title_fullStr | Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker |
| title_full_unstemmed | Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker |
| title_short | Agrin loss in Barrett's esophagus-related neoplasia and its utility as a diagnostic and predictive biomarker |
| title_sort | agrin loss in barrett s esophagus related neoplasia and its utility as a diagnostic and predictive biomarker |
| url | https://hdl.handle.net/1721.1/146811 |
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