Although in the last 50 years a significative reduction of gastric cancer cases has been observed, this disease remains one of the most important causes of world deaths. 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 carcino-genesis. Therefore, a proteomic and genomic approach on endoscopic bioptic samples of 45 dyspeptic patients (19 H. pylori-positive) and on 28 gastric cancer cases, was undertaken. Sequencing by MALDI-TOF led to identify, in gastric mucosa, several proteins. Among these, with respect to H. pylori-negative, in H. pylori-positive samples three proteins were up-regulated (RhoGDIα, IgJ, HSP27) and three others were down-regulated (RBP, GST, GKN1). The alteration of these proteins is in general related to carcino-genesis. 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 tumoral areas while, it was expressed in all non-tumoral cases. The present data could suggest that GKN1 may play a role in early phase of H. pylori-related gastric carcinogenesis.