Gastroenterology

Gastroenterology

Volume 131, Issue 3, September 2006, Pages 925-933
Gastroenterology

Microarrays and other new technology
Gene Expression Profiling Reveals Stromal Genes Expressed in Common Between Barrett’s Esophagus and Adenocarcinoma

https://doi.org/10.1053/j.gastro.2006.04.026Get rights and content

Background & Aims: Barrett’s esophagus is a precursor of esophageal adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene expression enhance the identification of specific genes as well as gene expression patterns that are expressed by Barrett’s esophagus and adenocarcinoma compared with normal tissues. Barrett’s esophagus length has also been identified as a risk factor for progression to adenocarcinoma, but whether there are intrinsic biological differences between short-segment and long-segment Barrett’s esophagus can be explored with microarrays. Methods: Gene expression profiles for endoscopically obtained biopsy specimens of Barrett’s esophagus or esophageal adenocarcinoma and associated normal esophagus and duodenum were identified for 17 patients using DNA microarrays. Unsupervised and supervised approaches for data analysis defined similarities and differences between the tissues as well as correlations with clinical phenotypes. Results: Each tissue displays a unique expression profile that distinguishes it from others. Barrett’s esophagus and esophageal adenocarcinoma express a unique set of stromal genes that is distinct from normal tissues but similar to other cancers. Adenocarcinoma also showed lower and higher expression for many genes compared with Barrett’s esophagus. No difference in gene expression was found between short-segment and long-segment Barrett’s esophagus. Conclusions: The genome-wide assessment provided by current DNA microarrays reveals many candidate genes and patterns not previously identified. Stromal gene expression in Barrett’s esophagus and adenocarcinoma is similar, indicating that these changes precede malignant transformation.

Section snippets

Samples and RNA Isolation

Unselected patients scheduled for endoscopic evaluation for Barrett’s esophagus or esophageal adenocarcinoma were enrolled to participate in the study. Biopsy specimens were obtained according to the Seattle protocol using a standard esophagogastroduodenoscope (Olympus GIF-XV10; Center Valley, PA) and biopsy forceps (Radial Jaw 3; Boston Scientific Corp, Natick, MA). Four biopsy specimens each were obtained from normal-appearing esophagus (proximal to Barrett’s esophagus), salmon-colored

Human Subjects and Cell Lines

Gene expression was evaluated for endoscopically derived tissues obtained from Barrett’s esophagus, esophageal adenocarcinoma, normal esophagus, and duodenum for 17 subjects (Table 1). One of 14 patients (sample 673) with Barrett’s esophagus exhibited high-grade dysplasia. Samples from Barrett’s esophagus adjacent to the tumor mass were obtained from 2 patients (samples B-1 and B-6).

Gene expression profiles were also determined for esophageal adenocarcinoma and squamous carcinoma cell lines.

Discussion

The expanded genome-wide coverage available with current microarrays was applied to normal, metaplastic, and neoplastic tissues. The resultant gene expression profiles were able to distinguish Barrett’s esophagus, duodenum, normal esophagus, and esophageal adenocarcinoma from each other. For 2 patients, the samples were apparently misclassified. Barrett’s esophagus is often heterogeneous, and because the pathology was inferred from an adjacent biopsy specimen, variations based on sampling error

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  • Cited by (0)

    Supported by National Institutes of Health grants R01 DK063624 (to A.W.L., G.T., and M.B.O.) and P30 DK56339 (Stanford Digestive Disease Center).

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