Association between Tim-3 and Gal-9 expression and gastric cancer prognosis

Abstract

The T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3)/galectin 9 (Gal-9) pathway, which serves a pivotal role in immune regulation, is similar to the programmed death (PD)-1/PD-ligand 1 pathway. Recent evidence has suggested that Tim-3 is differentially regulated in a variety of tumors and is a potential therapeutic target. The aim of the present study was to evaluate Tim-3 and Gal-9 expression and cluster of differentiation (CD)3+, CD8+ and forkhead box (FOX)p3+ T cell tumor.infiltration in gastric cancer, as well as their impact on prognosis. Tissue samples from 587 patients with gastric cancer were used to create a tissue microarray (TMA). The immune markers Tim-3, Gal-9, CD3, CD8 and FOXp3 were immunostained in the TMA, and correlations with clinicopathological findings and prognosis were analyzed. Several Gene Expression Omnibus gastric cancer databases and the K.M plotter website were used to analyze the association between the expression of Tim-3, Gal-9 and CD8A RNA and patient survival. The results demonstrated that Tim-3 was mainly expressed in immune cells, with minimal expression in gastric cancer cells. Its ligand, Gal-9, was significantly overexpressed in tumor cells. Tim-3 and Gal-9 expression and Foxp3+ T cell density were negatively associated with the patient overall survival (OS) rate. The density of CD8+ T cells was positively associated with the patient OS rate. Tim-3 expression and CD8+ T cell density were revealed to be independent prognostic factors for patients with gastric cancer.