[Correlation between clinical pathophysiologic factors and expression of orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer].
[Correlation between clinical pathophysiologic factors and expression of orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer].
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结直肠癌临床病理生理因素与乳清酸磷酸核糖转移酶（OPRT）、胸苷酸合酶（TS）、二氢嘧啶脱氢酶（DPD）表达的相关性
DOI：
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
M. Okano
中科院分区：
文献类型：
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作者：
T. Ochiai;M. Sugitani;K. Nishimura;H. Noguchi;Tomoo Watanabe;H. Sengoku;H. Komiyama;M. Okano
为了研究这些物质对氟化嘧啶抗癌药5-氟尿嘧啶（5-FU）作用的影响，我们测定了不同组织类型的羊角酸磷酸核糖基转移酶（OPRT）活性、胸苷酸合成酶（TS）酶活性和二氢嘧啶脱氢酶（DPD）活性。我们还研究了这3种酶与临床病理生理特征（年龄、性别、肿瘤侵袭程度、淋巴结转移程度、淋巴浸润、静脉浸润结肠壁）的相关性。对68例在我科行手术切除的结直肠癌患者进行了研究。与正常组织相比，肿瘤组织中OPRT活性显著升高（p < 0.01）。粘液癌患者肿瘤组织中OPRT活性水平最低，而低分化腺癌患者肿瘤组织中TS酶活性最高。DPD在低分化腺癌和黏液癌的肿瘤组织中也表现出较高的活性水平。与5-FU抗肿瘤作用相关的酶的表达可能是导致低分化腺癌和粘液癌患者预后不良的一个因素。在目前的临床病理生理特征研究中，我们发现淋巴结转移与OPRT肿瘤/正常（T/N）比显著降低相关。我们的研究结果表明，通过在手术前确定OPRT的T/N比率来预测淋巴转移是可能的。
We measured the activity of orotate phosphoribosyl transferase (OPRT), the amount of thymidylate synthase (TS) enzyme, and the activity of dihydropyrimidine dehydrogenase (DPD) for individual tissue types in order to study the contribution of these substances to the effects of the pyrimidine fluoride anticancer drug 5-fluorouracil (5-FU). We also studied the correlation between these 3 enzymes and clinical pathophysiologic characteristics (age, sex, extent of tumor invasion, extent of metastasis to the lymph nodes, lymphatic invasion and the venous invasion of the colorectal wall). Sixty-eight patients with colorectal carcinoma who had undergone surgical resection in our department were studied. There was a significant (p < 0.01) elevation of OPRT activity in the tumor tissue compared with regions of normal tissue. OPRT activity levels in the tumor tissue were lowest in patients with mucinous carcinoma while TS enzyme levels showed the highest activity in tumor tissue in poorly differentiated adenocarcinoma. DPD also showed high activity levels in tumor tissue in poorly differentiated adenocarcinoma and mucinous carcinoma. It is possible that the expression of enzymes with respect to the antitumor effects of 5-FU is a factor contributing to the poor prognosis for patients with poorly differentiated adenocarcinoma and mucinous carcinoma. In the present study of clinical pathophysiologic characteristics, we found that metastasis to the lymph nodes was associated with a significant reduction in the OPRT tumor/normal (T/N) ratio. Our results indicate that it may be possible to predict lymphatic metastasis by determining the T/N ratio for OPRT before surgery.