Komori Shuji, Osada Shinji, Tomita Hiroyuki, Nishio Kimitoshi, Kumazawa Iwao, Tachibana Susumu, Tsuchiya Juji, Yoshida Kazuhiro
Department of Surgical Oncology, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194; ; Department of Surgery, Ibi Welfare Hospital, Ibigawa, Gifu 501-0696;
Department of Surgical Oncology, Gifu University Graduate School of Medicine, Yanagido, Gifu 501-1194;
Mol Clin Oncol. 2013 May;1(3):453-460. doi: 10.3892/mco.2013.71. Epub 2013 Jan 17.
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.
了解结直肠癌（CRC）患者化疗前的化疗敏感性和副作用知识，可能有助于确保最佳的化疗效果。本研究的目的是确定对结直肠癌关键治疗药物5-氟尿嘧啶（5-FU）化疗敏感性的其他预测因素。对106例接受CRC治疗的患者手术获取的标本进行免疫组织化学评估，以研究5-FU代谢酶乳清酸磷酸核糖基转移酶（OPRT）、胸苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD）的蛋白表达与临床病理特征之间的相关性，以及蛋白表达与基于5-FU化疗结果之间的相关性。检测到5-FU代谢酶OPRT的高表达与阴性淋巴结转移之间存在相关性（P=0.0496），DPD与晚期肿瘤-淋巴结-转移（TNM）分级病例（IIIA-IVB）和阳性淋巴结转移之间也存在相关性（分别为P=0.0414）。在所有106例患者和79例接受基于5-FU化疗的患者中，OPRT表达阳性的患者生存率提高（分别为P=0.0144和0.0167）。在79例无复发患者中OPRT表达较高（P=0.0179），在接受R0手术和基于5-FU化疗且无副作用的患者中也较高（P=0.0126）。无副作用患者以及OPRT表达阳性且无副作用患者的无病生存率（DFS）较高（分别为P=0.0021和0.0031）。本研究结果表明，OPRT表达与基于5-FU化疗的较少副作用和患者较长生存期呈正相关。
