Objective To explore the expression and genotypes of thymidylate synthase (TS) in patients of non-small cell lung cancer (NSCLC) with different clinicopathological characteristics. Methods The expression profiles of TS were examined by immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in 160 patients with NSCLC. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect TS-5′UTR tandem repeats, G/C nucleotide polymorphisms, and 3′UTR 6 bp deletion/insertion polymorphisms. The relationships between clinicopathological characteristics and TS expression or genotypes were investigated through χ 2 test. Kaplan–Meier survival analysis was used to analyze the association between TS expression and overall survival (OS) and disease-free survival (DFS) of NSCLC patients. Results The expression levels of TS protein and TS gene in NSCLC tissues were significantly higher than that in paracancerous tissues ( P < 0.05). Furthermore, high expression of TS protein and 5′UTR polymorphism of TS gene showed significant correlation with differentiation, TNM stage, and lymph node metastases. The frequency of −6 bp/−6 bp genotypes in patients with NSCLC was 43.13% (69/160), which was higher than others. In addition, the rate of TS protein overexpression in NSCLC patients with 3R/3R was 79.79%, which was higher than others. Interestingly, high expression of TS protein predicted shorter DFS and OS and lower 3-year DFS rate and 3-year OS rate. Conclusions The expression levels of TS in NSCLC were significantly increased and may help to predict the prognosis of NSCLC, and high expression of TS protein and 5′UTR polymorphism of TS gene were significantly related to differentiation, TNM stage, and lymph node metastases.

中文翻译：

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不同临床病理特征的非小细胞肺癌患者胸苷酸合酶表达与基因型的相关性

目的探讨胸苷酸合酶（TS）在不同临床病理特征的非小细胞肺癌（NSCLC）患者中的表达及基因型。方法采用免疫组化染色和定量实时逆转录聚合酶链反应（qRT-PCR）检测160例NSCLC患者TS的表达谱。聚合酶链反应限制性片段长度多态性 (PCR-RFLP) 用于检测 TS-5'UTR 串联重复序列、G/C 核苷酸多态性和 3'UTR 6 bp 缺失/插入多态性。通过χ2检验研究临床病理特征与TS表达或基因型之间的关系。Kaplan-Meier 生存分析用于分析 TS 表达与 NSCLC 患者的总生存 (OS) 和无病生存 (DFS) 之间的关联。结果 NSCLC组织中TS蛋白和TS基因的表达水平显着高于癌旁组织（ P < 0.05）。此外，TS蛋白的高表达和TS基因的5'UTR多态性与分化、TNM分期和淋巴结转移显着相关。NSCLC患者-6 bp/-6 bp基因型的频率为43.13%（69/160），高于其他患者。此外，3R/3R NSCLC患者TS蛋白过表达率为79.79%，高于其他患者。有趣的是，TS 蛋白的高表达预测了较短的 DFS 和 OS，以及较低的 3 年 DFS 率和 3 年 OS 率。