A research group from the Department of Surgery, Division of Thoracic and Foregut Surgery, at the University of Southern California, in Los Angeles, USA, examined expression levels of several genes important in carcinogenesis, and compared expression levels with alterations in esophageal acid exposure.
Genetic changes associated with the progression to Barrett's esophagus and adenocarcinoma have previously been identified, but changes in gene expression associated with gastroesophageal reflux disease have not been reported, until now.
The research team carried out a prospective analysis of 61 patients initially seen with reflux symptoms at a private academic hospital.
| Only COX-2 gene expression levels correlated with increased esophageal acid exposure|
|Archives of Surgery|
Each patient had paired esophageal biopsy specimens of the squamous epithelium taken from 3 cm above the squamocolumnar junction.
24-hour ph monitoring was also performed on all of the subjects.
The biopsy samples were used to carry out messenger RNA expression analysis on snap-frozen, micro-dissected tissue using a quantitative reverse transcriptase-polymerase chain reaction method.
Genes tested for were cyclooxygenase (COX) 1, COX-2, thymidylate synthase, human telomerase reverse transcriptase (hTERT), Bcl-2 protein, survivin protein, secreted protein acidic and rich in cysteine (SPARC), tetraspan (TSPAN), and caudal-type homeobox transcription factor 2 (CDX2). These are all genes important in carcinogenesis.
Linear regression and the Pearson product moment correlation were used to relate gene expression to parameters of the 24-hour pH record.
These analyses identified expression levels of COX-2 as correlating positively with the 24-hour pH score, while there was no correlation between the expression of the other tested genes and esophageal acid exposure.
There proved to be no significant increase in COX-2 expression in patients with esophagitis or in patients using nonsteroidal anti-inflammatory drugs.
Dr Nahid Hamoui, one of the lead authors of the report, commented on their findings thus:
"To our knowledge, these data provide among the first reported correlation of genetic changes and increased esophageal acid exposure in patients with gastroesophageal reflux symptoms."
"The changes in gene expression occur before any metaplastic changes in the tissue are apparent, and may in the future be useful in predicting which patients will progress through a metaplasia-dysplasia carcinoma sequence."