Ochiai Takumi, Umeki Masahiko, Miyake Hiroshi, Iida Tatsumi, Okumura Minoru, Ohno Kazuhide, Sakamoto Masashi, Miyoshi Nobukazu, Takahashi Masahiko, Tsumura Hidenori, Tokunaga Yukihiko, Naitou Haruhiko, Fukui Takuji
Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
Department of Surgery, Hyogo Prefectural Awaji Medical Center, Hyogo 656-0021, Japan.
Oncol Rep. 2014 Sep;32(3):887-92. doi: 10.3892/or.2014.3299. Epub 2014 Jul 2.
Although 5-fluorouracil (5-FU) is an important drug for colorectal cancer (CRC) treatment, no useful biomarker is currently available to predict treatment response. Since 5-FU is converted into active or inactive forms by orotate phosphoribosyltransferase (OPRT) or dihydropyrimidine dehydrogenase (DPD), a correlation between these enzymes and response to 5-FU has been suggested. However, such a correlation has not been investigated prospectively. Therefore, in the present study, we aimed to prospectively evaluate whether OPRT and DPD were predictive factors of the response to 5-FU treatment in patients with resectable CRC. The present investigation was designed as a multicenter prospective cohort study. OPRT and DPD activities were assessed in biopsy samples, obtained surgically from patients with resectable CRC. The OPRT/DPD ratio was calculated and the cut-off values for this ratio were determined for 5-year disease-free survival (DFS) and overall survival (OS). Patients were treated with 5-FU/leucovorin (LV) regimens and oral 5-FU. The endpoint of this study was the correlation between the OPRT/DPD ratio and 5-year DFS and OS. The cut-off value for the OPRT/DPD ratio was determined by using the maximum χ2 statistic method against 5-year DFS and OS. Sixty-eight patients were enrolled from July 2003 to May 2005. The median follow-up period was 1925 days. The OPRT/DPD ratio cut-off values for 5-year DFS and OS were 0.015 and 0.013, respectively. During the 5-year DFS and OS periods, patients with higher cut-off values had a better prognosis than those with lower ratios (P=0.03 and 0.02, respectively). In conclusion, our results suggest that the OPRT/DPD ratio could be a predictive factor for response to 5-FU/LV adjuvant chemotherapy.
尽管5-氟尿嘧啶（5-FU）是治疗结直肠癌（CRC）的一种重要药物，但目前尚无有用的生物标志物可用于预测治疗反应。由于5-FU可通过乳清酸磷酸核糖基转移酶（OPRT）或二氢嘧啶脱氢酶（DPD）转化为活性或非活性形式，因此有人提出这些酶与对5-FU的反应之间存在相关性。然而，尚未对这种相关性进行前瞻性研究。因此，在本研究中，我们旨在前瞻性评估OPRT和DPD是否为可切除CRC患者对5-FU治疗反应的预测因素。本研究设计为一项多中心前瞻性队列研究。对从可切除CRC患者手术获取的活检样本中的OPRT和DPD活性进行评估。计算OPRT/DPD比值，并确定该比值的临界值以用于5年无病生存期（DFS）和总生存期（OS）。患者接受5-FU/亚叶酸（LV）方案和口服5-FU治疗。本研究的终点是OPRT/DPD比值与5年DFS和OS之间的相关性。通过使用针对5年DFS和OS的最大χ2统计方法确定OPRT/DPD比值的临界值。2003年7月至2005年5月共纳入68例患者。中位随访期为1925天。5年DFS和OS的OPRT/DPD比值临界值分别为0.015和0.013。在5年DFS和OS期间，临界值较高的患者比比值较低的患者预后更好（分别为P=0.03和0.02）。总之，我们的结果表明，OPRT/DPD比值可能是对5-FU/LV辅助化疗反应的预测因素。
