In a study from Korea, 10.2% of GCs were positive for mtMSI as well as 12.5% with dysplasia, associated with poor prognosis and high potential for progression [48]. On the “bacterial side”, the relationship of CagA and VacA genotypes to progression of preneoplastic gastric lesions was assessed in a Spanish population [49]. In 312 patients in a median follow-up of 12.8 years based on endoscopic surveillance, infection with a CagA-positive, VacA s1 and VacA m1 genotypes was associated with higher prevalence of preneoplastic lesions at time of inclusion as well as higher risk of progression of these lesions (OR 4.80; 95% CI 1.71–13.5) [49]. The duodenal ulcer promoting gene

A (dupA) represents a new potential virulence factor of H. pylori which is under evaluation

for its pathogenic power. In a retrospective cohort study from Japan including patients with peptic ulcer for a 14.4 years mean find more follow-up, presence of dupA was associated with lower GC incidence and lower acid output compared with dupA-negative subjects [50]. A meta-analysis on the association PLX4032 of dupA with different gastroduodenal diseases revealed regional differences in the related diseases. Whereas dupA seemed to have a protective effect for gastric ulcer (OR 0.2; 95% CI 0.1–0.4) and GC (OR 0.3; 95% CI 0.2–0.6) in South America, there was clear risk increase for subjects in China (gastric ulcer: OR 5.5, 95% CI 2.4–12.4; GC: OR 2.0, 95% CI 1.1.–3.1) [51]. However, there are also data

showing no association of dupA status with any gastroduodenal disease at all [52]. A new approach to identify disease-specific gene signature is the computational analysis of gene network associations after microarray analysis. So far, these high-throughput techniques have been applied to several cancer entities but also to nonmalignant pathologies like cardiovascular disease to identify molecular targets for the development of diagnostic as well as therapeutic means. A group from Korea recently performed oligonucleotide microarray analysis on samples from gastric adenocarcinoma and gastric adenoma, and normal mucosa as control [53]. By unsupervised hierarchical clustering analysis, they could show a differential gene expression between the three groups, and the combination with robust multicategory vector machines PIK3C2G revealed 39 and 21 genes that were gradually up- or downregulated in adenoma and carcinoma, respectively. Expression of selected genes was validated by RT-PCR and immunohistochemistry, like downregulation of trefoil factor peptide 2 (TFF2) during the progression from normal mucosa via adenoma and dysplasia toward invasive carcinoma [53]. TFF2 is responsible for mucosal repair mechanisms, and its function is generally regarded as tumor suppressive. Recently, TFF2 gene expression has reported to be downregulated by promotor hypermethylation which can be induced by H. pylori infection [54].