Prognostic value of 5-fluorouracil metabolic enzyme genes in Dukes' stage B and C colorectal cancer patients treated with oral 5-fluorouracil-based adjuvant chemotherapy.
5-Fluorouracil (5-FU) is the most commonly used anticancer drug for colorectal cancer (CRC). In this study, we aimed to clarify the prognostic value of the expression of the 5-FU metabolic enzyme genes, including orptate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD), thymidylate synthetase (TS) and thymidylate phosphorylate (TP) genes in CRC patients treated with oral 5-FU-based adjuvant chemotherapy. We examined 103 CRC patients with Dukes' stage B and C who underwent oral 5-FU-based adjuvant chemotherapy. Formalin-fixed, paraffin-embedded tumor specimens from primary CRC tissues were dissected by laser-captured microdissection and quantification of mRNA levels of OPRT, DPD, TS and TP were measured by real-time reverse transcription (RT) PCR. The relationship between these 5-FU metabolic enzyme gene levels and disease-free and overall survival rates were examined. The disease-free and overall survival curves of the OPRT mRNA high-expression group were significantly longer than that of the OPRT mRNA low-expression group. The disease-free and overall survival curves of the DPD mRNA high-expression group were significantly shorter than that of the DPD mRNA low-expression group. In contrast, there were no significant differences between the TS or TP mRNA high- expression and low-expression groups in the disease-free and overall survival curves. In a multivariate Cox regression analysis, it was demonstrated that the OPRT mRNA level is an independent prognostic variable for disease-free and overall survival. These results suggest that the OPRT mRNA is a useful indicator in the prediction of disease-free and overall survival in Dukes' B and C stage CRC patients treated with oral 5-FU-based adjuvant chemotherapy.
Yamada
Hideki
H
Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan.
Iinuma
Hisae
H
Watanabe
Toshiaki
T
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil