Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in tumor tissues and the efficacy of 5-fluorouracil in patients with non-small-cell lung cancer

Lung Cancer. 2004 Aug;45(2):189-96. doi: 10.1016/j.lungcan.2004.01.015.


We examined 116 stage I-IIIA non-small-cell lung cancer (NSCLC) patients for intra-tumoral expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) using TaqMan reverse transcription polymerase chain reaction (RT-PCR) assay to clarify the correlation between gene expression and the efficacy of 5-fluorouracil (5-FU) in patients with NSCLC. Patients who were administered 5-FU alone after surgery comprised the 5-FU group (n = 30), and those who underwent only surgery comprised the control group (n = 86). When dichotomized at the mean TS and DPD mRNA level, patients with low-DPD tumors who were administered 5-FU had a significantly better prognosis than those who did not receive adjuvant treatment (p = 0.041). In addition, in the 5-FU group, 10 patients with both low-TS and low-DPD tumors have not had any relapse, whereas 8 of the 20 patients with either high-TS or high-DPD tumors developed distant metastasis after surgery. Based on these results, the quantitation of TS and DPD mRNA levels may predict the efficacy of 5-FU after surgery for patient with NSCLC.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Base Sequence
  • Biomarkers, Tumor / analysis
  • Biopsy, Needle
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Case-Control Studies
  • Chemotherapy, Adjuvant
  • Chi-Square Distribution
  • Dihydrouracil Dehydrogenase (NADP) / analysis
  • Dihydrouracil Dehydrogenase (NADP) / metabolism*
  • Female
  • Fluorouracil / administration & dosage*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Staging
  • Probability
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Survival Analysis
  • Thymidylate Synthase / analysis
  • Thymidylate Synthase / metabolism*
  • Treatment Outcome


  • Biomarkers, Tumor
  • RNA, Messenger
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Fluorouracil