- 作者: Xia Wang, Yadi Wang, Yue Wang, Jian Cheng, Yanyun Wang and Minwen Ha
- 作者服務機構: Department of Oncology, First Affiliated Hospital of Liaoning Medical College, Jinzhou, China
- 中文摘要: --
- 英文摘要:
Background: Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair.
Altered expression of TS protein or TS gene polymorphisms has been associated with cancer
progression and treatment response. This study investigated the expressions of TS and its
gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to
pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected
NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein
and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung
adenocarcinoma patients were examined for polymorphisms of the TS gene 3’-UTR 1494del 6bp, which was then investigated for associations with responses of the patients to
pemetrexed treatment and survival.
Results: Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with
matched normal tissues, and significantly higher in lung squamous cell carcinoma than in
lung adenocarcinoma. TS expression was associated with poor tumor differentiation.
Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the
TS gene 3’-UTR 1494 bp (−6bp/-6bp) genotype and the rest had TS gene 3’-UTR 1494 bp
(−6bp/+6bp). There was no TS 3’-UTR 1494 bp (+6bp/+6bp) genotype in any patients.
Statistical analysis revealed that gender, tumor stage, and TS 3’-UTR 1494del 6bp
polymorphism were significant prognostic factors after short-term pemetrexed treatment.
Log-rank analysis revealed that patients with the (−6bp/-6bp) genotype had significantly
better progression-free and overall survival than patients with (−6bp/+6bp).
Conclusions: This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of
TS 3’-UTR 1494del 6bp are associated with sensitivity of lung adenocarcinoma patients to
pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated
as prognostic markers for personalized therapy in lung adenocarcinoma. - 中文關鍵字: --
- 英文關鍵字: Lung adenocarcinoma, Non-small cell lung cancer, Pemetrexed treatment, Thymidylate synthase, TS gene polymorphism