Serum soluble Tim‑3 is elevated in patients with cervical cancer and is higher in advanced clinical stages.

Abstract

T-cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule that is expressed generally on the cell membrane of immune and cancer cells and is implicated as a negative regulator of anti-tumour immune responses; this occurs through the interaction of Tim-3 with galectin-9. Although the function of membrane Tim-3 is well known, the role of soluble Tim-3 (sTim-3) has been poorly explored. The aim of the present study was to compare the serum levels of sTim-3 in the cervical cancer group of patients vs. the control group, to determine the association between the serum levels of sTim-3 with the clinicopathological characteristics of patients with cervical cancer and with serum galectin-9 levels. The concentrations of serum sTim-3 and galectin-9 were determined using ELISA. A receiver operating characteristic (ROC) curve was performed to determine the diagnostic value of sTim-3. The Mann-Whitney and Kruskall-Wallis tests were used to compare the serum sTim-3 concentrations between the control and cervical cancer groups and among the clinical subgroups. The association between the concentrations of sTim-3 and galectin-9 was determined using Spearman's rank correlation coefficient. sTim-3 expression was higher in patients with cervical cancer compared with control patients. The ROC curve revealed that sTim-3 has diagnostic potential, with a specificity of 95% and a sensitivity of 85.19%. sTim-3 was higher in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IV compared with those with FIGO stages I, II and III. A moderate positive correlation (ρ=0.41) was identified between sTim-3 and galectin-9. This was the first report of changes in the serum concentrations of sTim-3 in patients with cervical cancer and their diagnostic value. The association between sTim-3 with cervical cancer progression, and the positive correlation between the serum concentrations of sTim-3 and galectin-9 suggested that both proteins might be involved in the immune dysregulation in cervical cancer, but this requires further exploration.