Transcriptome signatures in Helicobacter pylori-infected mucosa identifies acidic mammalian chitinase loss as a corpus atrophy marker
- Equal contributors
1 Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
2 Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
3 National Cancer Center, Singapore, Singapore
4 Department of Microbiology and Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
5 Genome Institute of Singapore, Singapore, Singapore
6 Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
BMC Medical Genomics 2013, 6:41 doi:10.1186/1755-8794-6-41Published: 11 October 2013
The majority of gastric cancer cases are believed to be caused by chronic infection with the bacterium Helicobacter pylori, and atrophic corpus gastritis is a predisposing condition to gastric cancer development. We aimed to increase understanding of the molecular details of atrophy by performing a global transcriptome analysis of stomach tissue.
Biopsies from patients with different stages of H. pylori infection were taken from both the antrum and corpus mucosa and analyzed on microarrays. The stages included patients without current H. pylori infection, H. pylori-infected without corpus atrophy and patients with current or past H. pylori-infection with corpus-predominant atrophic gastritis.
Using clustering and integrated analysis, we found firm evidence for antralization of the corpus mucosa of atrophy patients. This antralization harbored gain of gastrin expression, as well as loss of expression of corpus-related genes, such as genes associated with acid production, energy metabolism and blood clotting. The analyses provided detailed molecular evidence for simultaneous intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) in atrophic corpus tissue. Finally, acidic mammalian chitinase, a chitin-degrading enzyme produced by chief cells, was shown to be strongly down-regulated in corpus atrophy.
Transcriptome analysis revealed several gene groups which are related to development of corpus atrophy, some of which were increased also in H. pylori-infected non-atrophic patients. Furthermore, loss of acidic chitinase expression is a promising marker for corpus atrophy.