title: Beyond Field Effect: Analysis of Shrunken Centroids in Normal Esophageal Epithelia Detects Concomitant Esophageal Adenocarcinoma.
abstract: BACKGROUND AND AIMS: Because of the extremely low neoplastic progression rate in Barrett's esophagus, it is difficult to diagnose patients with concomitant adenocarcinoma early in their disease course. If biomarkers existed in normal squamous esophageal epithelium to identify patients with concomitant esophageal adenocarcinoma, potential applications would be far-reaching. The aim of the current study was to identify global gene expression patterns in normal esophageal epithelium capable of revealing simultaneous esophageal adenocarcinoma, even located remotely in the esophagus. METHODS: Tissues comprised normal esophageal epithelia from 9 patients with esophageal adenocarcinoma, 8 patients lacking esophageal adenocarcinoma or Barrett's, and 6 patients with Barrett's esophagus alone. cDNA microarrays were performed, and pattern recognition in each of these subgroups was achieved using shrunken nearest centroid predictors. RESULTS: Our method accurately discriminated normal esophageal epithelia of 8/8 patients without esophageal adenocarcinoma or Barrett's esophagus and of 6/6 patients with Barrett's esophagus alone from normal esophageal epithelia of 9/9 patients with Barrett's esophagus and concomitant esophageal adenocarcinoma. Moreover, we identified genes differentially expressed between the above subgroups. Thus, based on their corresponding normal esophageal epithelia alone, our method accurately diagnosed patients who had concomitant esophageal adenocarcinoma. CONCLUSIONS: These global gene expression patterns, along with individual genes culled from them, represent potential biomarkers for the early diagnosis of esophageal adenocarcinoma from normal esophageal epithelia. Genes discovered in normal esophagus that are differentially expressed in patients with vs. without esophageal adenocarcinoma merit further pursuit in molecular genetic, functional, and therapeutic interventional studies.
authors.affiliation: Gastroenterology Division, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD 21231.
authors.forename: Florin M
authors.initials: FM
authors.lastname: Selaru
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Yin
authors.forename: Karsten
authors.initials: K
authors.lastname: Schulmann
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Mori
authors.forename: Alexandru V
authors.initials: AV
authors.lastname: Olaru
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: James P
authors.initials: JP
authors.lastname: Hamilton
authors.forename: John M
authors.initials: JM
authors.lastname: Abraham
authors.forename: Paul
authors.initials: P
authors.lastname: Schneider
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Greenwald
authors.forename: Jan
authors.initials: J
authors.lastname: Brabender
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer