Gastric cancer is a world health problem and depicts the fourth leading mortality cause from malignancy in Mexico. Causation of gastric cancer is not only due to the combined effects of environmental factors and genetic variants. Recent molecular studies have transgressed a number of genes involved in gastric carcinogenesis. The aim of this review is to understand the recent basics of gene expression in the development of the process of gastric carcinogenesis. Genetic variants, polymorphisms, desoxyribonucleic acid methylation, and genes involved in mediating inflammation have been associated with the development of gastric carcinogenesis. Recently, these genes (interleukin 10, Il-17, mucin 1, β-catenin, CDX1, SMAD4, SERPINE1, hypoxia-inducible factor 1 subunit alpha, GSK3β, CDH17, matrix metalloproteinase 7, RUNX3, RASSF1A, TFF1, HAI-2, and COX-2) have been studied in association with oncogenic activation or inactivation of tumor suppressor genes. All these mechanisms have been investigated to elucidate the process of gastric carcinogenesis, as well as their potential use as biomarkers and/or molecular targets to treatment of disease.

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.

Currently, the only available vaccine against tuberculosis is Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary tuberculosis protection provided by the vaccine varies depending on the strain, the patient’s age and the evaluated population. Although the adaptive immune responses induced by different BCG strains have been widely studied, little conclusive data is available regarding innate immune responses, especially in macrophages. Here, we aimed to characterize the innate immune responses of human THP-1-derived macrophages at the transcriptional level following a challenge with either the BCG Mexico (M.BCG) or Phipps (P.BCG) strains. After a brief in vitro characterization of the bacterial strains and the innate immune responses, including nitric oxide production and cytokine profiles, we analyzed the mRNA expression patterns and performed pathway enrichment analysis using RNA microarrays. Our results showed that multiple biological processes were enriched, especially those associated with innate inflammatory and antimicrobial responses, including tumor necrosis factor (TNF)-α, type I interferon (IFN-I) and IFN-γ. However, four DEGs were identified in macrophages infected with M.BCG compared to P. BCG. These findings indicated the proinflammatory stimulation of macrophages induced by both BCG strains, at the cytokine level and in terms of gene expression, suggesting a differential expression pattern of innate immune transcripts depending on the mycobacterial strain.

Chronic Helicobacter pylori infection produces several lesions in the human stomach, which can progress to chronic atrophic gastritis and gastric cancer. To date, there is very little information on gene expression in chronic atrophic gastritis and its relationship with progression to gastric cancer. In this study, we performed a gene expression analysis during chronic atrophic gastritis in order to identify possible biomarkers that allow an early diagnosis of gastric cancer. We studied biopsies from patients with chronic atrophic gastritis and gastric cancer. The biopsies were analyzed by a gene expression microarray and corroborated by qPCR and validated through immunohistochemistry. Our results revealed that gene expression profiles in patients with chronic atrophic gastritis showed molecular changes of the gastric mucosa, leading to gastric cancer. The gene expression profiles of CLDN1, CLDN7, OLFM4, C-MYC and MMP9 were more notable from the chronic atrophic gastritis. The gene expression patterns observed in this study allowed the identification of CLDN1 and MMP9 proteins as promising biomarkers of early stages of gastric cancer development.