Details

Autor(en) / Beteiligte

• Cui, Sai‐Jin
• Li, Yan
• Zhou, Rong‐Miao
• Liu, Lu
• Cao, Shi‐Ru
• Huang, Xi
• Huo, Xiang‐Ran
• Wang, Na

Titel

TIM‐3 polymorphism is involved in the progression of esophageal squamous cell carcinoma by regulating gene expression

Ist Teil von

• Environmental and molecular mutagenesis, 2021-04, Vol.62 (4), p.273-283

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2021

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• The T‐cell immunoglobulin and mucin domain containing molecule 3 (TIM‐3), a crucial immune regulatory molecule, is an emerging immune checkpoint target for cancer therapy. Our study aimed to investigate the association between TIM‐3 polymorphisms (rs10053538 C > A, rs10515746 C > A, and rs1036199 A > C) and the susceptibility and prognosis of esophageal squamous cell carcinoma (ESCC). We further detect the effects of polymorphisms on TIM‐3 expression. Two independent case–control sets (population‐based and hospital‐based sets) were performed in total 994 ESCC patients and 998 controls. TIM‐3 polymorphisms were genotyped by polymerase chain reaction‐ligase detection reaction (PCR). Survival data were available for 198 patients who received platinum‐based chemotherapy after surgery. The regulation on TIM‐3 expression by the polymorphisms was investigated in 35 patients using real‐time quantitative PCR. The association between mRNA level of TIM‐3 and survival was detected by using Kaplan–Meier plotter database. We found that for rs10053538 C > A polymorphisms, A allele was associated with significant increased risk of ESCC (odds ratios [OR] = 1.34, 95%CI = 1.05–1.72), and CA/AA genotypes enhanced susceptibility to ESCC for smokers (adjusted OR = 1.61, 95%CI = 1.00–2.59). The patients with AA genotypes had significantly poor prognosis (adjusted HR = 4.98, 95%CI = 1.14–21.71). The patients carrying CA/AA genotypes had significantly higher mRNA levels of TIM‐3 than those carrying the CC genotype. Furthermore, high mRNA level of TIM‐3 had a shorter overall survival in patients (HR = 2.56, 95%CI = 1.04–6.28). For rs10515746 C > A and rs1036199 A > C polymorphisms, there were no statistical correlation with the progression of ESCC. These data demonstrate that rs10053538 C > A polymorphisms may be associated with the susceptibility and prognosis of ESCC patients through regulating expression of TIM‐3.