This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Joshi, N. Articles by Kirsch, I. R. Search for Related Content PubMed PubMed Citation Articles by Joshi, N. Articles by Kirsch, I. R.

Gene Expression Differences in Normal Esophageal Mucosa Associated with Regression and Progression of Mild and Moderate Squamous Dysplasia in a High-Risk Chinese Population

¹ Genetics Branch, Center for Cancer Research and ² Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI); ³ Office of Clinical and Regulatory Affairs, National Center for Complementary and Alternative Medicine and ⁴ Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NIH; ⁵ Office of Centers, Training, and Resources, NCI, NIH, Bethesda, Maryland; ⁶ Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China; and ⁷ Mayo Clinic College of Medicine, Rochester, Minnesota

Requests for reprints: Philip R. Taylor, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, EPS, 6120 Executive Boulevard, Room 7006, Bethesda, MD 20892-7236. Phone: 301-594-2932; Fax: 301-402-4489; E-mail: ptaylor{at}mail.nih.gov.

A randomized, double-blinded, placebo-controlled 2 x 2 factorial chemoprevention trial was conducted in Linxian, China to assess the effects of selenomethionine and celecoxib on the natural history of esophageal squamous dysplasia. Results from this study indicated that asymptomatic adults with mild dysplasia were more likely to show an improvement when treated with selenomethionine compared with placebo (P = 0.02). Prompted by this finding, we examined the molecular profiles associated with regression and progression of dysplastic lesions in normal mucosa from 29 individuals, a subset of the Linxian cohort, using the Affymetrix U133A chip. Twenty differentially expressed genes were associated with regression and 129 were associated with progression when we compared the change in gene expression over time. Genes associated with immune response (n = 15), cell cycle (n = 15), metabolism (n = 15), calcium transport or calcium ion activity (n = 10), regulation of transcription (n = 9), signal transduction (n = 7), cytoskeleton and microtubules (n = 5), nucleotide processing and biosynthesis (n = 4), G-coupled signaling (n = 4), and apoptosis (n = 3) were present in the list of 149 genes. Using the Expression Analysis Systematic Explorer pathway analysis program, only the immune response pathway was significantly overrepresented among these 149 genes. Individuals whose lesions regressed seemed to have higher expression of genes associated with immune stimulation, such as antigen presentation, survival of T cells, and T-cell activation (HLA-DRA, HLA-DPA1, HLA-DBQ1, CD58, and FCER1A). In contrast, individuals whose lesions progressed had higher expression of genes involved in immune suppression and inflammation (CNR2, NFATC4, NFRKB, MBP, INHBB, CMKLR1, CRP, ORMS, SERPINA7, and SERPINA1). These data suggest that local and systemic immune responses may influence the natural history of esophageal squamous dysplasia. (Cancer Res 2006; 66(13): 6851-60)

This article has been cited by other articles:

				S. R. Mallery, J. C. Zwick, P. Pei, M. Tong, P. E. Larsen, B. S. Shumway, B. Lu, H. W. Fields, R. J. Mumper, and G. D. Stoner Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions Cancer Res., June 15, 2008; 68(12): 4945 - 4957. [Abstract] [Full Text] [PDF]

				V. Pagmantidis, C. Meplan, E. M van Schothorst, J. Keijer, and J. E Hesketh Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes Am. J. Clinical Nutrition, January 1, 2008; 87(1): 181 - 189. [Abstract] [Full Text] [PDF]