Background: Recurrence is the leading cause of treatment failure and death in patients
with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and
prognostic markers are still lacking.
Methods: We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1
year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence.
Then, the biological effects of these genes on gastric cancer were studied.
Results: A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate
gene whose DNA methylation was higher in GC samples from patients with shorter survival and
lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer
survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced
expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown
of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced
cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal
transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of
Conclusion: These results suggest that MDP1 protein suppresses the survival of gastric cancer cells
and loss of MDP expression may benefit the recurrence of gastric cancer.