title: Prognostic impact of orotate phosphoribosyl transferase among 5-fluorouracil metabolic enzymes in resectable colorectal cancers treated by oral 5-fluorouracil-based adjuvant chemotherapy.
abstract: Orotate phosphoribosyl transferase (OPRT) is the main enzyme that involves in phosphoribosylation of 5-fluorouracil (5-FU), an essential step that leads to tumor growth inhibition. In our study, the prognostic relevance of OPRT, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in resectable colorectal cancer (CRC) patients treated by oral 5-FU were compared to further clarify the prognostic value of OPRT. Tumor tissue was collected from 90 CRC patients and the patients were followed for 5.2 years (Median). TS, DPD and OPRT activities in the extract of tumor tissue were determined enzymatically. The cut-off value of OPRT (0.147 nmol/(min mg), TS (0.044 pmol/mg) and DPD (72.10 pmol/(min mg) were determined by maximal chi(2) method. Among these 5-FU metabolic enzymes, only high OPRT group demonstrated significantly better disease-free survival (DFS) (p = 0.0152) and better overall survival (p = 0.0078). In Cox regression analysis, node status (p < 0.0005) and OPRT (p = 0.044) were significant factors for DFS. OPRT activity in tumor tissue was a predictor of prognosis in resectable CRC patients treated by oral 5-FU-based adjuvant chemotherapy, and was useful to pick-up high risk patients independent from known prognosis factors.
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Japan. takumi-o@ma.kitanet.ne.jp
authors.forename: Takumi
authors.initials: T
authors.lastname: Ochiai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishimura
authors.forename: Hajime
authors.initials: H
authors.lastname: Noguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Akira
authors.initials: A
authors.lastname: Tsukada
authors.forename: Emiko
authors.initials: E
authors.lastname: Watanabe
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
authors.forename: Shunji
authors.initials: S
authors.lastname: Futagawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009962:Orotate Phosphoribosyltransferase / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil