title: Decreased galectin-9 and increased Tim-3 expression are related to poor prognosis in gastric cancer.
abstract: BACKGROUND
  Galectin-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.
  
  
  METHODS
  Gal-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.
  
  
  RESULTS
  Gal-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).
  
  
  CONCLUSIONS
  The 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.
authors: Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, China.
authors: Jing
authors: J
authors: Jiang
authors: Mei-Shan
authors: MS
authors: Jin
authors: Fei
authors: F
authors: Kong
authors: Donghui
authors: D
authors: Cao
authors: Hong-Xi
authors: HX
authors: Ma
authors: Zhifang
authors: Z
authors: Jia
authors: Yin-Ping
authors: YP
authors: Wang
authors: Jian
authors: J
authors: Suo
authors: Xueyuan
authors: X
authors: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D037161:Galectins / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins