Translation of gastric disease progression at gene level expression

Abstract

Helicobacter pylori is associated with the development of several lesions in the human stomach. This chronic infection produces gastritis, which can progress to intestinal metaplasia and gastric cancer. To date, there is very little information regarding gene-expression in the different phases of progression caused by chronic H. pylori infection. In this study, we performed a genome-wide gene-expression analysis in gastric biopsies of patients chronically infected with H. pylori, using the potential of high-throughput technologies that have not been fully exploited in this area. Here we illustrate the potential correlation of H. pylori infection with the gene expression changes in follicular gastritis, chronic gastritis and intestinal metaplasia. We also suggest its potential as biomarkers of each condition. An exploratory set of 21 biopsies from patients with follicular gastritis, chronic gastritis, and intestinal metaplasia were analyzed by gene-expression microarrays in order to identify the biological processes altered in each lesion. The microarray data was corroborated by real-time PCR, while 79 Formalin-Fixed Paraffin-Embeded samples were analyzed by immunohistochemistry. Follicular gastritis exhibited significant enrichment in genes associated with glutamate signaling, while chronic gastritis showed a down-regulation in metallothionein 1 and 2 and in oxidative phosphorylation-related genes, which could be associated with the chronic infecton of H. pylori. Intestinal metaplasia exhibited an over-expression of gastrointestinal stem cell markers, such asLGR5 and PROM1, as well as messenger RNA and nucleic acid metabolism-related genes. The gene-expression patterns found in this study provide new comparative information about chronic gastritis, follicular gastritis and intestinal metaplasia that may play an important role in the development of gastric cancer.

Molecular Mechanisms Contributing Bacterial Infections to the Incidence of Various Types of Cancer

“…Patients with a history of H. pylori infection underwent annual endoscopic observation after eradication and were screened for novel markers such as gastric epithelium released tissue, protein biomarkers, and other proteins associated with cellular metaplasia in dysplasia in carcinoma. Other markers such as CD44, a signalling molecule in cell proliferation and differentiation, and metallopeptidase, an immune response-mediated marker, were also assayed (Table 1) [39,40]. Metaplastic intestinal cells are characterized by overexpression of gastrointestinal stem cell markers like PROM1 gene product, leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), and genes related to the metabolism of messenger RNA and nucleic acids [39].…”

“…Other markers such as CD44, a signalling molecule in cell proliferation and differentiation, and metallopeptidase, an immune response-mediated marker, were also assayed (Table 1) [39,40]. Metaplastic intestinal cells are characterized by overexpression of gastrointestinal stem cell markers like PROM1 gene product, leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), and genes related to the metabolism of messenger RNA and nucleic acids [39].…”

Comprehensive Integration of Genome-Wide Association and Gene Expression Studies Reveals Novel Gene Signatures and Potential Therapeutic Targets for Helicobacter pylori-Induced Gastric Disease

“…Further gene expression studies from human patients and experimental models have elucidated many of the molecular mechanisms relevant to H. pylori pathogenicity and the pathways related to the various disease stages. However, their results remain indecisive as they show a variable picture, most likely due to low sample numbers in individual studies or variations in disease stage and severity in analyzed samples ( 7 , 8 ). A powerful model to study a tissue and cell specific reaction to H. pylori especially at the different stages of the pathology is the use of cell lines or animal models.…”

Copy number alterations and epithelial-mesenchymal transition genes in diffuse and intestinal gastric cancers in Mexican patients

“…Currently, there are few published studies involving genotyping of GC samples employing high-density microarrays (13)(14)(15); however, in those altered chromosomes, gains and losses have a phenotypic impact, and different signaling pathways are involved. The presence of CNA changes the genetic dose and would modify several molecular mechanisms as epithelialmesenchymal transition (EMT), which is the transformation of epithelial to mesenchymal cells and a critical stage for the transition to metastasis (16).…”

“…Reports of CNA events involving Latin American populations are still scant (23,24). In fact, at present there are few studies of GC genotyping by whole-genome high-density microarrays in Mexican patients (14,15). Therefore, our study aimed to determine CNA in DGC and IGC to identify through bioinformatics analyses, the main genes and signaling pathways involving EMT-genes.…”