The TIM-3 Rs10053538 Polymorphism Is Associated with Clinical Prognosis of Colorectal Cancer

ABSTRACT

Background

Genetic variants in the T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) gene have been reported to be associated with the risk of cancers and patients’ outcomes. The aims of this study were to explore the role of TIM-3 polymorphisms in the risk of colorectal cancer (CRC) and the prognosis of CRC patients in a northern Chinese population.

Methods

Two polymorphisms of TIM-3 were genotyped using polymerase chain reaction and ligase detection reaction in 364 CRC patients and 372 healthy control subjects. The levels of TIM-3 mRNA were investigated in 65 CRC tissues by quantitative real-time PCR.

Results

The results showed that neither rs10053538 nor rs10515746 was associated with susceptibility to CRC. However, the CA+AA genotypes of rs10053538 were related to an advanced clinical stage and increased risk of lymph nodemetastasis (P = .046 and 0.024, respectively). Multivariate analyses performed after adjusting for clinical variables showed that patients with the CA+AA genotypes of rs10053538 exhibited a significantly shorter disease-free survival (DFS) and overall survival (OS) time compared with those carrying the CC genotype (HR = 1.91, 95% CI = 1.04–3.51; HR = 2.61, 95% CI = 1.35–5.03). In addition, the expression of TIM-3 mRNA was significantly increased in the CRC tissues of patients carrying the rs10053538 CA+AA genotypes compared with patients carrying the CC genotype (P = .019).

Conclusion

The rs10053538 may serve as an independent molecular marker for predicting the clinical outcome of CRC patients in the study population.

KEYWORDS:

• Colorectal cancer
• polymorphism
• prognosis
• risk
• TIM-3

Acknowledgments

The authors would like to acknowledge several doctors in the Department of General Surgery of the Fourth Hospital of Hebei Medical University, China, for their assistance in recruiting study participants.

Author contributions

DK, YL, and YD designed the study and carried out the experiments. DK, YL and NY recruited the patients and collected the data. YL, YD and BL analysed the data and prepared draft figures and tables. All authors were involved in writing the paper and provided final approval of the submitted and published versions.

Ethics approval and consent to participate

The present study was approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University (Hebei, China) and written informed consent was obtained from all individuals.

Competing interests

The authors have no conflicts of interest to declare.

Consent for publication

All study participants provided written informed consent for the data to be published.

Additional information

Funding

This work was supported by a grant from the Health Commission of Hebei Province (Hebei, China; grant no. 20180558)..