Changes:Gene Expression/Intermed Endpoints:Gastric

#A115 Changes in Gene Expression in Intermediate Endpoints of Gastric Cancer: A Randomized, Placebo-Controlled Trial of Helicobacter pylori Eradication Therapy.

Chiao-Jung Tsai,1 Shufang Yang,1 Robert J. Tibshirani,1 Jeannette Guarner,2 Alejandro Mohar,3 Roberto Herrera-Goepfert,3 Julie Parsonnet.

1 Stanford University School of Medicine,1 Stanford, CA, Centers for Disease Control and Prevention,2 Atlanta, GA, Instituto Nacional de Cancerologia,3 Tlalpan, Mexico.

Aim: We hypothesized that Helicobacter pylori (HP) eradication could decrease gastric cancer risk. To determine if this was the case we used microarray technology to assess changes in gene expression in patients with preneoplastic conditions after HP eradication therapy.

Methods: We used archived tissues from a randomized placebo-controlled trial of HP eradication conducted on subjects with gastric preneoplastic lesions in Chiapas, Mexico.

A total of 20 subjects 10 from the treatment arm and 10 from the placebo arm were selected. A pair of pre- and post-treatment gastric tissue biopsies from each of the 20 subjects was analyzed using cDNA microarray.

Significant Analysis of Microarrays (SAM) was employed to analyze the gene expression data. Genes that showed more than two-fold over- or under-expression between groups were considered to have significantly different expression.

Results: Treatment and placebo groups had similar gene expressions prior to HP eradication therapy (0 gene differed). One year after treatment, 27 genes differed between the two groups, with a median false-discovery rate (FDR) of 6.7% (i.e., of the 27 genes, 1.8 of them were expected to show marked over- or under-expression by chance; 1.8/27 = 6.7%).

When using a paired analysis to compare the pre- and post-treatment tissues from the same individuals in the placebo group, we found that 69 genes expressed differently after the one-year period, with a 9.3% FDR.

In contrast, there was minimal change in the treatment arm over the one-year period (5 genes expressed differently, with a 0% FDR).

Therefore, the differences in gene expression between the treatment and placebo groups were largely accounted for by changes over time in the placebo group. Genes whose expressions became up-regulated over time in the placebo arm included a member of trefoil factor family and other genes associated with cellular adhesion, tumor-related signal transduction, and tight junction.

Genes that became down-regulated included genes associated with cell-cycle regulation, inflammation, and other immune responses.

Conclusion: We observed changes in gastric gene expression over one years time in individuals with preneoplastic conditions who received no HP eradication therapy.

In contrast, only minimal changes in gene expression were observed in those who received HP eradication therapy. This suggests that HP eradication may interrupt evolution of gastric preneoplasia.

AACR Frontiers in Cancer Prevention Research, 2003

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