Gastric cancer is still one of the prevalent leading causes of cancer-related deaths
worldwide. The high mortality rate is mainly due to late-stage diagnosis, which has a very
poor prognosis (five-year survival rates are as little as 3-10%). By contrast, early stage
gastric cancer is highly curable with five-year survival rates exceeding 90%. Early
detection is therefore the single most important factor influencing the outcome for gastric
cancer patients. However, there are currently no biomarkers of acceptable sensitivity and
specificity to detect early stage gastric cancer. Gastric infection with Helicobacter pylori
(H. pylori) seems to be a risk factor for gastric cancer. Epidemiological studies have shown
that patients that test serum positive to H. pylori infection are associated with a three- to
six-fold increase in the risk of gastric cancer, findings that are compatible with pathological
links between H. pylori-associated gastritis, pre-cancerous lesions, and subsequent cancer
of the stomach. In a previous study, moving from genomic to proteomic investigation, we
have identified a protein, gastrokine 1 (GKN1), a stomach-secreted protein previously
named AMP-18 (18kDa Antrum Mucosa Protein) that was highly expressed in normal
tissues and significantly down-regulated in H. pylori positive patients with respect to H.
pylori negative subjects. In addition, we have also found that GKN1 is normally expressed
in gastric mucosa but not in primary tumours, both at the transcriptional and translational
levels. On the basis of these findings, we propose that GKN1 can be used as a new
molecular marker that could be useful to predict early cell transformation and might be a
potential novel target for gastric cancer therapeutics. Moreover, we have also found that
recombinant GKN1 affect cancer cell growth and that the transient expression of GKN1
in human gastric cancer also inhibits cell growth and induces apoptosis, thus suggesting the
importance of GKN1 in preventing cancer development in gastric tissues. Finally, we
hypothesize that GKN1 might act as a tumor suppressor and thus foresee its importance as
an antitumor drug.
Keywords: Gastrokine-1, non-atrophic gastritis, chronic atrophic gastritis,
intestinal metaplasia, dysplasia, Gastric Cancer, prognostic biomarker, cDNA
microarrays, gene expression, mRNA, Helicobacter pylori, Fas, Fas ligand,
Caspase-3, Apoptosis.
