Clinical significance of expression of Hint1 and potential epigenetic mechanism in gastric cancer.

HINT1, a member of the evolutionary highly conserved HIT protein superfamily, is ubiquitously expressed in diverse species including mammalian tissues. Accumulating evidence shows that HINT1 is a haploinsufficient tumor suppressor. In the present study, we explored possible correlations between the expression level of HINT1 and clinicopathological features in tissues from gastric cancer (GC) patients. Decreased expression of HINT1 detected by qPCR and Western blotting in tumor tissues was found in 58.82 and 39.2% of the patients, respectively. Significantly reduced expression of HINT1 was found in poorly differentiated tumor tissues (p=0.027). Environmental interference (either H. pylori or EBV infection) (p=0.005) was associated with the expression of HINT1. Moreover, compared with the GC tissues, the level of Hint1 detected by qPCR was significantly higher in the adjacent non-cancerous tissues (p=0.03). We treated AGS cells, a GC cell line with low expression level of HINT1, with 5 and 10 μmol/l 5-Aza-dC for 72 h and found that HINT1 could be induced by 5-Aza-dC in a dose-dependent manner. These results suggested that Hint1 expression was lower in GC tissues and some etiological factors, such as H. pylori/EB infection or promoter hypermethylation may play a role in gastric tumorigenesis.