Gene expression differences in normal esophageal mucosa associated with regression and progression of mild and moderate squamous dysplasia in a high-risk Chinese population

Nina Joshi, Laura Lee Johnson, Wen Qiang Wei, Christian C. Ahnet, Zhi Wei Dong, Philip R. Taylor, Paul John Limburg, Sanford M. Dawsey, Ernest T. Hawk, You Lin Qiao, Ilan R. Kirsch

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A randomized, double-blinded, placebo-controlled 2 × 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.

Original languageEnglish (US)
Pages (from-to)6851-6860
Number of pages10
JournalCancer Research
Volume66
Issue number13
DOIs
StatePublished - Jul 1 2006

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Selenomethionine
Gene Expression
Celecoxib
Natural History
Population
Genes
HLA-DR alpha-Chains
Placebos
Calcium
T-Lymphocytes
Chemoprevention
Antigen Presentation
Cytoskeleton
Microtubules
Signal Transduction
China
Cell Cycle
Mucous Membrane
Nucleotides
Ions

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gene expression differences in normal esophageal mucosa associated with regression and progression of mild and moderate squamous dysplasia in a high-risk Chinese population. / Joshi, Nina; Johnson, Laura Lee; Wei, Wen Qiang; Ahnet, Christian C.; Dong, Zhi Wei; Taylor, Philip R.; Limburg, Paul John; Dawsey, Sanford M.; Hawk, Ernest T.; Qiao, You Lin; Kirsch, Ilan R.

In: Cancer Research, Vol. 66, No. 13, 01.07.2006, p. 6851-6860.

Research output: Contribution to journalArticle

Joshi, Nina ; Johnson, Laura Lee ; Wei, Wen Qiang ; Ahnet, Christian C. ; Dong, Zhi Wei ; Taylor, Philip R. ; Limburg, Paul John ; Dawsey, Sanford M. ; Hawk, Ernest T. ; Qiao, You Lin ; Kirsch, Ilan 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. In: Cancer Research. 2006 ; Vol. 66, No. 13. pp. 6851-6860.
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abstract = "A randomized, double-blinded, placebo-controlled 2 × 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.",
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AU - Joshi, Nina

AU - Johnson, Laura Lee

AU - Wei, Wen Qiang

AU - Ahnet, Christian C.

AU - Dong, Zhi Wei

AU - Taylor, Philip R.

AU - Limburg, Paul John

AU - Dawsey, Sanford M.

AU - Hawk, Ernest T.

AU - Qiao, You Lin

AU - Kirsch, Ilan R.

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