Prognostic value of TIM-1 expression in human non-small-cell lung cancer

Abstract

Background T-cell immunoglobulin and mucin domain 1 (TIM-1) is an important co-stimulatory molecule which serves as a surface marker for T cell activation, especially for Th2 cells. Recently, many studies have also shown that TIM-1 can be abnormally expressed in human cancers and may have a potential role in promoting cancer progression. Methods The immunohistochemistry was used to examine the TIM-1 expression in human non-small-cell lung carcinoma (NSCLC) tissues. The cellular studies were performed to investigate the role of TIM-1 in the regulation of biological functions of human lung cancer cell lines. Results We found that the TIM-1 expression was increased in human NSCLC tissues compared with the adjacent normal tissues, and the OS rate of NSCLC patients with higher TIM-1 expression was significantly lower compared with the ones with lower TIM-1 expression. The COX model showed that higher TIM-1 expression in lung cancer tissues could be used as an independent prognostic predictor for the patients. Furthermore, we depleted TIM-1 in NSCLC cell lines A549 and SK-MES-1, and the cellular functional studies also revealed that depletion of TIM-1 could significantly inhibit the cell viability as well as the abilities of migration and invasion. In addition, our microarray data showed that certain signaling pathways were altered and enriched after depletion of TIM-1. We subsequently verified that PI3K/Akt signaling pathway was involved in the TIM-1-mediated regulation of cellular functions in NSCLC cells. Conclusion Our findings supported the notion that TIM-1 could serve as a potential therapeutic target for NSCLC.

Comprehensive Analysis of the Expression, Relationship to Immune Infiltration and Prognosis of TIM-1 in Cancer

“…Moreover, the overall survival rate of non-small-cell lung cancer patients with high expression of TIM-1 is significantly lower than that of patients with low expression of TIM-1. In cell experiments, it was also found that inhibition of TIM-1 expression could inhibit the migration and invasion ability of A549 and SK-MES-1 cells in vitro, respectively (43). All these suggest that TIM-1 plays an important role in the invasion and metastasis of cancers.…”

<p>Knockdown of T Cell Immunoglobulin and Mucin 1 (Tim-1) Suppresses Glioma Progression Through Inhibition of the Cytokine-PI3K/AKT Pathway</p>

“…11 Studies have identified that Tim-1 is expressed in many human tumor tissues. 19,20,29,30 Tim-1 is presented in cancer cells, in CD68-positive macrophages and CK-18-positive epithelial cells 29 in human Langerhans cell sarcoma. Liu et al 30 have revealed Tim-1 levels in human gastric cancer tissues are upregulated, indicating the prognostic application of Tim-1 in gastric cancer patients.…”

“…Zheng et al found down-regulation of Tim-1 caused by RNA interference could block cellular events of NSCLC cells. 20 Accordingly, Tim-1 is an underlying therapeutic target for human cancers.…”

“…22 A recent study has also verified that PI3K/AKT axis is involved in the Tim-1-mediation of cellular functions in NSCLC cells. 20 Furthermore, we used an activator SC97 of the PI3K/AKT pathway to identify its molecular mechanism in glioma. When SC79 was combined with knockdown Tim-1, the malignant behaviors and the secretion levels of cytokines in glioma cells were significantly increased.…”

“…19 Recently, the prognostic significance of Tim-1 expression has been reported in human non-small-cell lung cancer (NSCLC). 20 But the biological functions of Tim-1 in glioma remain elusive. Therefore, this study attempted to mainly evaluate the expression and regulatory roles of Tim-1 in glioma.…”