Decreased galectin-9 and increased Tim-3 expression are related to poor prognosis in gastric cancer

• Published in: PloS one Vol. 8; no. 12; p. e81799
• Main Authors: Jiang, Jing, Jin, Mei-Shan, Kong, Fei, Cao, Donghui, Ma, Hong-Xi, Jia, Zhifang, Wang, Yin-Ping, Suo, Jian, Cao, Xueyuan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.12.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Apoptosis; Cancer; Cancer metastasis; Cancer research; Cancer treatment; Carcinogenesis; Carcinogens; Cell Line, Tumor; Colorectal surgery; Correlation analysis; Cytokines; Disease-Free Survival; Epidemiology; Female; Galectin-9; Galectins - biosynthesis; Gastric cancer; Gene Expression Regulation, Neoplastic; Health aspects; Hepatitis A Virus Cellular Receptor 2; Humans; Immunohistochemistry; Immunoregulation; Lymph; Lymph nodes; Lymphatic Metastasis; Lymphocytes T; Male; Medical prognosis; Melanoma; Membrane Proteins - biosynthesis; Metastases; Metastasis; Middle Aged; Mucin; Mucosa; Multivariate analysis; Neoplasm Proteins - biosynthesis; Pathology; Patients; Polyclonal antibodies; Prognosis; Protein expression; Proteins; Retrospective Studies; Rodents; Stomach cancer; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Studies; Survival Rate; T cells; Tumor cells; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081799

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. 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. 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). 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.