Downregulated Tim-3 expression is responsible for the incidence and development of colorectal cancer

Abstract

The present study aimed to investigate the role of T cell immunoglobulin domain and mucin-3 (Tim-3) in its gene and protein forms in colorectal cancer (CRC), and to verify the significance of Tim-3 expression in patients with CRC. A prospective analysis of 258 patients with CRC and 246 normal controls was conducted between December 2012 and June 2015. Intestinal samples were collected, including of CRC tissues, paracancerous tissues and normal colon mucosa tissues. Peripheral venous blood samples were also collected. Polymerase chain reaction (PCR) amplification, reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis was performed for the detection and evaluation of Tim-3 gene and protein in various tissues. PCR analysis indicated that the T and G alleles of-882C/T and 4259T/G are associated with a significantly increased risk of CRC. Following the confirmation of Tim-3 expression in CRC tissues, RT-qPCR detection and western blot analysis revealed clear downregulation of Tim-3 mRNA and protein expression in the blood and tissue samples obtained from patients with CRC, as compared with in the corresponding control samples. Similar trends of decreased Tim-3 mRNA levels and protein expression were observed in CRC tissues compared with in the paracancerous and the normal colon mucosa tissues. In addition, the mRNA and protein expression levels in the paracancerous tissues were lower than those in the normal colon mucosa tissues. Furthermore, significantly lower Tim-3 mRNA levels were observed in patients with a tumor size >5 cm, a poor differentiation degree, higher tumor-node-metastasis stage (stage III-IV), and lymph node and distant metastasis. Collectively, genetic changes to Tim-3, expressed as polymorphisms in Tim-3, and decreased mRNA/protein expression may be partially responsible for the incidence and development of CRC.