Are GKN1 and GKN2 genes distinctive diagnostic markers for gastric cancer? A molecular investigation

Gastric cancer (GC) has high incidence and mortality rate in several countries and is still one of the most frequent and lethal diseases. The evolution of intestinal tumors is characterized by progression of several sequential steps that start with gastritis and then progresses to mucosal atrophy, intestinal metaplasia, dysplasia and carcinoma with subsequent metastatic dissemination. Novel mitogenic and motogenic Gastrokine1 (GKN1) and Gastrokine 2 (GKN2) genes that are highly expressed in normal stomach epithelium and plays an important role in maintaining the integrity and homeostasis of stomch mucosal epithelial cells. Significant loss of copy number and mRNA transcript of GKN1 and GKN2 gene expression were frequently observed in all type of gastric cancer. In this study, 47 paired samples that were grouped according to the types of gastric cancer and the clinical characteristics of the patients, including gender and average of age were investigated with gene expression analysis, SSCP technique and nucleotide sequencing. Both GKN1 and GKN2 genes were observed significantly reduced. (Wilcoxon signed rank test; p<0,05). As a result of gene screening; no mutation (no different genotype) was detected. It is considered that gen mutations are not the cause of inactivation of gastrokines. In conclusion; the mRNA expression level of gastrokine genes was decreased regardless the gender, age or cancer type of patients. Down-regulation of GKN genes seems to occur at the initial steps of cancer development. This preliminary data must be confirmed by further analysis like immunohistochemistry, epigenetic analysis, miRNA analysis, and western blot. Keywords: Gastric cancer, GKN1, GKN2, expression analysis, mutation screening.