Changes of protein expression in Helicobacter pylori-infected human gastric mucosa.

Although in the last 50 years, a significant reduction of gastric cancer cases has been observed, this disease remains one of the most important causes of deaths around the world. Infection with Helicobacter pylori is the main risk factor of gastric cancers. However, despite numerous epidemiological studies, the association between H. pylori infection and gastric cancer (GC) still remains unexplained thus, prevention is most likely the means for reducing the burden of this disease. Our investigation was aimed to define possible molecular markers implicated in H. pylori-related carcinogenesis. Therefore, a proteomic and genomic approach was undertaken on endoscopic biopsy samples of 45 dyspeptic patients (19 H. pylori-positive) and on 28 gastric cancer cases. Sequencing by MALDI-TOF led to identify several proteins in the gastric mucosa. Among these, with respect to H. pylori-negative, in H. pylori-positive samples three proteins were up-regulated (RhoGDI?, IgJ, HSP27) and three others were down-regulated (RBP, GST, GKN1). The alteration of these proteins is in general related to carcinogenesis. Interestingly, two isoforms of GKN1, differing in the first N-terminal amino acid residue, were also identified. In the H. pylori-negative group, both isoforms were always present whereas, a lower expression of the GKN1 basic isoform in a subgroup of H. pylori-positive patients with severe gastritis, was found. In addition, GKN1 was completely absent in all tumoural areas while, it was expressed in all non-tumoural cases. The present data could suggest that GKN1 may play a role in the early phase of H. pylori-related gastric carcinogenesis.