Association of expression and genotypes of thymidylate synthase in non-small cell lung cancer patients with different clinicopathological characteristics

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 chi(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 by/-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, NM stage, and lymph node metastases.