Predictive value of orotate phosphoribosyltransferase in colorectal cancer patients receiving 5‑FU‑based chemotherapy

Komori,Shuji; Osada,Shinji; Tomita,Hiroyuki; Nishio,Kimitoshi; Kumazawa,Iwao; Tachibana,Susumu; Tsuchiya,Juji; Yoshida,Kazuhiro

doi:10.3892/mco.2013.71

Predictive value of orotate phosphoribosyltransferase in colorectal cancer patients receiving 5‑FU‑based chemotherapy

Authors:
- Shuji Komori
- Shinji Osada
- Hiroyuki Tomita
- Kimitoshi Nishio
- Iwao Kumazawa
- Susumu Tachibana
- Juji Tsuchiya
- Kazuhiro Yoshida
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Affiliations: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194, Japan, Department of Oncological Pathology, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194, Japan, Department of Surgery, Ibi Welfare Hospital, Ibigawa, Gifu 501-0696, Japan
Published online on: January 17, 2013 https://doi.org/10.3892/mco.2013.71
Pages: 453-460

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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.

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