IntroductionGalectin-9 (Gal-9) induces adhesion and aggregation of certain cell types and inhibits the metastasis of tumor cells. T-cell immunoglobulin–and mucin domain-3–containing molecule 3 (TIM-3) plays a pivotal role in immune regulation. The aim of this study is to investigate Gal-9 and TIM-3 alterations in gastric cancer and their prognostic values.MethodsGal-9 and Tim-3 expression was evaluated using a tissue microarray immunohistochemistry method in 305 gastric cancers, of which 84 had paired adjacent normal samples. Cell lines SGC-7901, BGC-823, MGC-803, MKN45 and GES-1 were also stained. Correlations were analyzed between expression levels of Gal-9 and Tim-3 protein and tumor parameters or clinical outcomes.ResultsGal-9 and Tim-3 stained positive on tumor cells in 86.2% (263/305), and 60.0% (183/305) patients with gastric cancer, respectively. Gal-9 expression was significantly higher in cancer than in normal mucosa (P<0.001). Reduced Gal-9 expression was associated with lymph-vascular invasion, lymph node metastasis, distant metastasis and worse TNM staging (P = 0.034, P = 0.009, P = 0.002 and P = 0.043, respectively). In contrast, Tim-3 expression was significantly lower in cancer than in control mucosa (P<0.001). Patients with lymph-vascular invasion had higher expression levels of Tim-3 (P<0.001). Moreover, multivariate analysis shows that both high Gal-9 expression and low Tim-3 expression were significantly associated with long overall survival (P = 0.002, P = 0.010, respectively); the combination of Gal-9 and Tim-3 expression was an independent prognostic predictor for patients with gastric cancer (RR: 0.43; 95%CI: 0.20–0.93). H.pylori infection status was not associated with Gal-9 and Tim-3 expression (P = 0.102, P = 0.565).ConclusionThe results suggest that expression of Gal-9 and Tim-3 in tumor cells may be a potential, independent prognostic factor for patients with gastric cancer. Gal-9 and TIM-3 may play an important part in the gastric carcinogenesis.

Gastrokine 1 (GKN1) plays a role in the gastric mucosal defence mechanism and may be a gastric tumour suppressor. We have investigated whether inactivation of the GKN1 gene is involved in the development and/or progression of gastric cancers. GKN1 protein expression was examined in gastric adenomas and cancer and we also analysed GKN1 mutation and epigenetic alteration, DNA copy number change and mRNA transcript expression. The effect of GKN1 on cell proliferation and death was examined in wild-type GKN1-transfected AGS gastric cancer cells. Reduced or loss of GKN1 expression was detected in 36 (90%) and 170 (89.5%) of 40 adenomas and 190 gastric cancers, respectively. Statistically, there was no significant relationship between altered expression of GKN1 protein and clinicopathological parameters, including depth of invasion, location and lymph node metastasis (χ(2) test, p > 0.05). In western blot analysis, absence or reduced expression was found in 21 (84.0%) of 25 gastric carcinomas. No mutation was detected in gastric tumours, and hypermethylation of GKN1 gene was found in two tumours. DNA copy number and mRNA transcript of GKN1 were significantly decreased in gastric cancers. In functional analysis, AGS gastric cancer cells transfected with GKN1 wild-type showed marked inhibition of cell proliferation and induction of cell death. These data suggest that inactivation of the GKN1 gene may play an important role in the development of sporadic gastric cancers, as an early event.

The results suggest that expression of DNMT3a is an independent poor prognostic indicator in gastric cancer. DNMT3a might play an important role in gastric carcinogenesis.

Up to date, miR-137 has been demonstrated as a tumor suppressor in many kinds of human malignancies. In the present study, we conducted transfection, western blot and RT-PCR to explore the role of miR-137 in the development of human glioblastoma (GBM). Here, we found that miR-137 expression was obviously down-regulated in GBM tissues and cells rather than matched non-tumor tissues and NHA cells. However, the expression of C-X-C motif ligand 12 (CXCL12) mRNA and protein were up-regulated in GBM tissues and cells. In vitro, miR-137 mimics inhibited GBM cell proliferation, migration and invasion, and the 3′-untranslated regions (3′-UTR) of CXCL12 were a direct target of miR-137. In addition, miR-137 mimics also inhibited the expression of EGFR, Bcl-2 and MMP2/9 proteins, but increased the expression of Bax protein. Notably, CXCL12 over-expression attenuated miR-137-inhibited cell proliferation and invasion, while CXCL12 siRNAs promoted miR-137 inhibition effects. In vivo, miR-137 mimics also suppressed tumor growth in nude mice xenograft model. In conclusion, miR-137 serves as a tumor suppressor by inhibition of CXCL12 in human GBM. Thus, miR-137-CXCL12 can be recommended as a useful and effective target for treatment of GBM.

Our results indicated that the expression of Ki-67 could be used as an independent prognostic factor for GIST patients.