title: Predictive value of orotate phosphoribosyltransferase in colorectal cancer patients receiving 5-FU-based chemotherapy.
abstract: Pretreatment knowledge of chemosensitivity and side-effects of chemotherapy for colorectal cancer (CRC) patients are likely to ensure the best chemotherapeutic outcome. The aim of this study was to identify additional predictive factors of chemosensitivity to the key CRC treatment drug 5-fluorouracil (5-FU). Surgically obtained specimens from 106 patients treated for CRC were immunohistochemically assessed to investigate the correlation between the protein expression of the 5-FU metabolic enzymes orotate phosphoribosyltransferase (OPRT), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD), and clinicopathological characteristics as well as the correlation between the protein expression and outcomes of 5-FU-based chemotherapy. A correlation was detected between the high expression of the 5-FU metabolic enzyme OPRT and negative lymph node metastasis (P=0.0496), as well as between DPD and advanced Tumor-Node-Metastasis (TNM) grade cases (IIIA-IVB) and positive lymph node metastases (P=0.0414, respectively). In all 106 patients and in 79 patients undergoing 5-FU-based chemotherapy, survival was improved in those patients with a positive OPRT expression (P=0.0144 and 0.0167, respectively). OPRT expression was higher in the 79 patients with no recurrence (P=0.0179) as well as in patients treated with R0 surgery and 5-FU-based chemotherapy without side-effects (P=0.0126). Disease-free survival (DFS) rate was higher in patients without side-effects, and in patients with a positive OPRT expression without side-effects (P=0.0021 and 0.0031, respectively). Findings of this study demonstrated that OPRT expression positively correlated with fewer side-effects of 5-FU-based chemotherapy and longer patient survival.
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194; ; Department of Surgery, Ibi Welfare Hospital, Ibigawa, Gifu 501-0696;
authors.forename: Shuji
authors.initials: S
authors.lastname: Komori
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194;
authors.forename: Shinji
authors.initials: S
authors.lastname: Osada
authors.affiliation: Department of Oncological Pathology, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Department of Surgery, Ibi Welfare Hospital, Ibigawa, Gifu 501-0696;
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Nishio
authors.affiliation: Department of Surgery, Ibi Welfare Hospital, Ibigawa, Gifu 501-0696;
authors.forename: Iwao
authors.initials: I
authors.lastname: Kumazawa
authors.affiliation: Department of Surgery, Ibi Welfare Hospital, Ibigawa, Gifu 501-0696;
authors.forename: Susumu
authors.initials: S
authors.lastname: Tachibana
authors.affiliation: Department of Surgery, Ibi Welfare Hospital, Ibigawa, Gifu 501-0696;
authors.forename: Juji
authors.initials: J
authors.lastname: Tsuchiya
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194;
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
keywords: 5-fluorouracil-based chemotherapy; orotate phosphoribosyltransferase; prognosis; side-effect