Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

Abstract

Pathogenic mechanisms associated with Helicobacter pylori infection enhance susceptibility of the gastric epithelium to carcinogenic conversion. We have characterized the gene expression profiles of gastric biopsies from 69 French Caucasian patients, of which 43 (62%) were infected with H. pylori. The bacterium was detected in 27 of the 42 antral biopsies examined and in 16 of the 27 fundic biopsies. Infected biopsies were selected for the presence of chronic active gastritis, in absence of metaplasia and dysplasia of the gastric mucosa. Infected antral and fundic biopsies exhibited distinct transcriptional responses. Altered responses were linked with: (1) the extent of polymorphonuclear leukocyte infiltration, (2) bacterial density, and (3) the presence of the virulence factors vacA, babA2, and cagA. Robust modulation of transcripts associated with Toll-like receptors, signal transduction, the immune response, apoptosis, and the cell cycle was consistent with expected responses to Gram-negative bacterial infection. Altered expression of interferon-regulated genes (IFITM1, IRF4, STAT6), indicative of major histocompatibility complex (MHC) II-mediated and Th1-specific responses, as well as altered expression of GATA6, have previously been described in precancerous states. Upregulation of genes abundantly expressed in cancer tissues (UBD, CXCL13, LY96, MAPK8, MMP7, RANKL, CCL18) or in stem cells (IFITM1 and WFDC2) may reveal a molecular switch towards a premalignant state in infected tissues. Tissue microarray analysis of a large number of biopsies, which were either positive or negative for the cag-A virulence factor, when compared to each other and to noninfected controls, confirmed observed gene alterations at the protein level, for eight key transcripts. This study provides 'proof-of-principle' data for identifying molecular mechanisms driving H. pylori-associated carcinogenesis before morphological evidence of changes along the neoplastic progression pathway. Modern Pathology (2007) 20, 974-989;

Protein interaction network related to Helicobacter pylori infection response

“…Microarray data were used to determine the global gene expression of infected cells. Microarray data showed up/down regulation of gene expression related to immune response, cell cycle, cell growth, and signal transduction, which may support the hypothesis that H pylori infection causes cancer development [4,11,13,20] . However, the data did not present a clear mechanism of carcinogenesis in a systematic manner.…”

“…The expression of genes significantly changed (P < 0.05) by H pylori infection in the microarray [4,11,13,20] data was examined, and genes related to the immune response were identified and collected. A total of 39 filtered genes (Table 1) were obtained.…”

“…However, the exact mechanism between H pylori and gastric carcinoma is unclear [19] . Various tools have been employed to identify the relationship between H pylori and gastric cancer, including c-DNA microarrays [4,20] . However, most of these methods did not consider the systematic interaction of biological components.…”

Analysis of whole genomic expression profiles ofHelicobacter pylorirelated chronic atrophic gastritis with IL‐1B‐31CC/‐511TT genotypes

“…This study suggests that a premalignant molecular signature can be detected in the most severely infected cases before any histological evidence of malignancy. 25 We identified 32 significant GO term annotations mainly involved in the intracellular biosynthetic process, the cellular biosynthetic process, phosphorylation, the purine ribonucleotide biosynthetic process, the purine nucleotide biosynthetic process, the ribonucleotide biosynthetic process, the purine ribonucleotide metabolic process, the purine nucleotide metabolic process and the ribonucleotide metabolic process. It has been reported that a large number of GO term annotations have taken part in gastric cancer development.…”

“…19 Results from Figure 1 also revealed that a total of 124 genes were differentially expressed between H. pylori-positive and -negative groups in six CAG samples with IL-1B-31CC/-511TT genotypes, and the samples of antral mucosa were divided correctly into two clusters by these genes. Hofman et al 25 have characterized the gene expression profiles of 42 antral biopsies corresponding to 27 patients infected with H. pylori. A total of 165 genes (92 upregulated and 73 downregulated) were defined as being differentially expressed between the gastric antrum of H. pylori-infected and non-infected patients.…”