title: Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas.
abstract: The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies.
authors.affiliation: Cancer Biology, Program in Biomedical Science, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Daysha
authors.initials: D
authors.lastname: Ferrer-Torres
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Nancarrow
authors.affiliation: Center for Cancer Biostatistics, Department of Biostatistics, School of Public Health, Ann Arbor, Michigan, USA.
authors.forename: Rork
authors.initials: R
authors.lastname: Kuick
authors.affiliation: Department of Pathology and Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.affiliation: Medical Oncology Department, Catalan Institute of Oncology, Barcelona, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Nadal
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Jules
authors.initials: J
authors.lastname: Lin
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chang
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Rishindra M
authors.initials: RM
authors.lastname: Reddy
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Orringer
authors.affiliation: Center for Cancer Biostatistics, Department of Biostatistics, School of Public Health, Ann Arbor, Michigan, USA.
authors.forename: Jeremy M G
authors.initials: JM
authors.lastname: Taylor
authors.affiliation: Department of Medicine and Department of Biomedical Engineering, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Wang
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D062465:Claudin-3 / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D004943:Esophagogastric Junction / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D023281:Genomics / Q000379:methods*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation
chemical_list: C568122:CLDN3 protein, human; D015820:Cadherins; D062465:Claudin-3; C573420:ICAM1 protein, human; D018799:Intercellular Adhesion Molecule-1; C086960:osteoblast cadherin
keywords: early detection; esophageal adenocarcinoma; gastroesophageal junction adenocarcinomas; molecular biomarkers