Micro-RNA (miR) Expression in Upper Gastrointestinal Mucosal Tissue

NCT ID: NCT00909350

Last Updated: 2015-02-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 10 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2008-11-30

Brief Summary

This is a laboratory-based, exploratory study using tissue obtained from our clinical practice. The purpose of this study is to confirm our ability to characterize miR expression in various tissues (proximal and distal esophagus, stomach and duodenum) obtained from the upper gastrointestinal tract in preparation for the study of MiR in patients with Barrett's esophagus and other inflammatory conditions of the upper gastrointestinal tract.

Detailed Description

The incidence of esophageal adenocarcinoma has increased dramatically over the past three decades. These adenocarcinomas usually arise from columnar lined epithelium of the esophagus known as Barrett's esophagus (BE). There is an established association between gastroesophageal reflux disease (GERD) and the development of BE and esophageal adenocarcinoma. In an attempt to diagnose esophageal adenocarcinoma at an earlier and more treatable stage, efforts have been directed at identifying patients with BE and enrolling them in surveillance protocols. Several authors have challenged this strategy since it has not yet been proven to save lives and is very expensive. A major unresolved problem is the fact that the clinical factors considered to be somewhat predictive of the presence or absence of BE are neither sufficiently sensitive nor specific. In addition, once BE is identified, predicting who may or may not progress to cancer is far from perfect. A molecular understanding of why certain patients develop BE and why certain of those progress to cancer is of obvious importance.

The molecular pathway from normal esophageal mucosa to Barrett's esophagus and on to adenocarcinoma is not well understood. Micro-RNA (miR) RNAs have recently emerged as important regulators of carcinogenesis and have not been studied in BE. We seek to confirm our ability to characterize miR expression in various tissues (esophagus, stomach and duodenum) obtained from the upper gastrointestinal tract in preparation for the study of MiR in patients with Barrett's esophagus and other inflammatory conditions of the upper gastrointestinal tract.

This study will involve collection of tissue via endoscopic biopsy in 10 patients with normal endoscopic appearance from the esophagus, stomach and duodenum. Ambion miR oligonucleotide arrays will be utilized to profile miRs that are specifically expressed in epithelial biopsies from the duodenum, stomach, and esophagus. Total RNA will be extracted from independent biopsy samples using the mirVana(R) micro RNA isolation kit from Ambion. The Ambion Flash PAGE(R) electrophoresis system will be used to resolve mature miRs from the larger pre-miR species. Mature miRs will be labeled and hybridized to Ambion mirVana miR(R)arrays, which will be scanned to identify miRs that are regulated under these circumstances. Signals from the microarrays will be processed using the R functions of Bioconductor for normalization and background correction and RMA for summarization. Statistical significance will be determined using Insightful S+ functions and assuming a least pooled error model. Potential targets will be confirmed by northern blotting. The routine histology sample will be reviewed simply to exclude other, unexpected microscopic pathology. Benign histologic findings such as minor inflammation, will not exclude the patient from inclusion. If there is a wide variation in miR expression, then the histology might be needed to help explain such variation.

Conditions

Barrett's Esophagus; Esophageal Adenocarcinoma

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

No treatment

genetic research project; to meet inclusion criteria, participants must have normal upper GI tract upon upper endoscopy, for study biopsies to be taken

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• willingness to give consent
• normal gross appearance of the esophagus, stomach and duodenum

Exclusion Criteria

• contraindication to mucosal biopsy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Kenneth R. DeVault, M.D.

Professor and Chair, Department of Medicine, Mayo Clinic, Jacksonville Florida

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kenneth R. DeVault,, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic, Jacksonville, Florida

Locations

Mayo Clinic

Jacksonville, Florida, United States

Countries

United States

Other Identifiers

06-005272

Identifier Type: -

Identifier Source: org_study_id