Prognostic impact of orotate phosphoribosyl transferase activity in resectable colorectal cancers treated by 5-fluorouracil-based adjuvant chemotherapy
Prognostic impact of orotate phosphoribosyl transferase activity in resectable colorectal cancers treated by 5-fluorouracil-based adjuvant chemotherapy
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DOI：
10.1002/jso.20553
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发表时间：
2006-07-01
影响因子：
2.5
通讯作者：
Futagawa, Shunji
中科院分区：
文献类型：
--
作者：
Ochiai, Takumi;Nishimura, Kazuhiko;Futagawa, Shunji
背景和目的：5-氟尿嘧啶 (5-FU) 的磷酸核糖基化是导致肿瘤生长抑制的重要步骤，乳清酸磷酸核糖基转移酶 (OPRT) 是参与 5-FU 转化为 5-氟尿苷单磷酸的主要酶。本回顾性研究旨在评估接受基于口服 5-FU 的辅助化疗治疗的结直肠癌 (CRC) 患者中肿瘤 OPRT 活性与临床结果之间的相关性。 方法：从 124 例可切除的 CRC 患者中获取手术标本，这些患者随后接受基于口服 5-FU 的辅助化疗。通过酶法测定肿瘤组织提取物中的 OPRT 活性。通过最大卡方 2 方法确定肿瘤内 OPRT 活性相对于无病生存的截止值。采用Kaplan-Meier法计算各组的无病生存率和总生存率。 结果：根据确定的瘤内OPRT临界值（0.147 nmol/min/mg蛋白质）将患者分为两组（高组：n = 102，低组：n = 22）。高 OPRT 组的五年 DFS (P = 0.035) 和 OS (P = 0.020) 明显更好。 结论：本研究表明，肿瘤 OPRT 测定有助于确定基于 5-FU 的辅助化疗结果，在临床实践中的应用应在基于 5-FU 的辅助化疗之前纳入肿瘤分析。
Background and Objectives: Phosphoribosylation of 5-fluorouracil (5-FU) is an essential step which leads to tumor growth inhibition and orotate phosphoribosyl transferase (OPRT) is the main enzyme that involves in this conversion of 5-FU to 5-fluorouridine monophosphate. This retrospective study was aimed to evaluate the correlation between tumor OPRT activity and the clinical outcome in colorectal cancer (CRC) patients treated by oral 5-FU-based adjuvant chemotherapy.Methods: Surgical specimen was obtained from resectable 124 CRC patients who were subsequently treated by oral 5-FU-based adjuvant chemotherapy. OPRT activity in the extract of tumor tissue was enzymatically determined. The cut-off value of intratumor OPRT activity against disease free survival was determined by maximal chi 2 method. The disease free survival and overall survival in each group were calculated using the Kaplan-Meier method.Results: Patients were divided into two groups by determined cut-off value of intratumor OPRT (0.147 nmol/min/mg protein) (high group: n = 102, low group: n = 22). Five-year DFS (P = 0.035) and OS (P = 0.020) were significantly better for high OPRT roup.Conclusions: This study demonstrated that an assay of tumor OPRT contributes to the determination of 5-FU-based adjuvant chemotherapy outcome and application in clinical practice should be included in tumor analysis prior to 5-FU-based adjuvant chemotherapy.