Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in tumor tissues and the efficacy of 5-fluorouracil in patients with non-small-cell lung cancer.
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.
Shintani
Yasushi
Y
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, E1, 2-2 Yamadaoka, Suita, 565-0871, Japan.
Ohta
Mitsunori
M
Hirabayashi
Hirohisa
H
Tanaka
Hisaichi
H
Iuchi
Keiji
K
Nakagawa
Katsuhiro
K
Maeda
Hajime
H
Kido
Tetsuo
T
Miyoshi
Shinichiro
S
Matsuda
Hikaru
H
D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology* / Q000401:mortality; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000032:analysis / Q000378:metabolism*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil