Matrix metalloproteinases in gastric inflammation and cancer : clinical relevance and prognostic impact

Abstract

The studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric cancer. In patients with H. pylori-induced gastritis, significantly increased mucosal MMP-9 levels were found. By successful H. pylori eradication, active and chronic inflammation decreased, accompanied by a significant decrease of mucosal MMP-9. MMP-2, MMP-7, MMP-8 and MMP-9, lipocalin-2, MMP-9/lipocalin-2 and TIMP-1 were significantly increased in tumour tissue of gastric cancer patients compared to normal gastric mucosa whereas only enhanced levels of MMP-2 and MMP-9/lipocalin-2 complexes were independently related to worse prognosis. Subsequently the genotype distribution of single-nucleotide polymorphisms (SNPs) of MMPs and TIMPs in gastric cancer was studied. The genotype distribution of MMP-7-181A>G was associated with H. pylori status and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2-303C>T correlated significantly with tumour-related survival. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7-181A>G and TIMP-2-303C>T polymorphism combination to have a major impact on patients survival outcome.</p