Nakayama Yoshifumi, Inoue Yuzuru, Nagashima Nobuo, Katsuki Takefumi, Matsumoto Kentarou, Kadowaki Koji, Shibao Kazunori, Tsurudome Yosuke, Hirata Keiji, Sako Tatsuhiko, Nagata Naoki, Itoh Hideaki
Department of Surgery 1, University of Occupational and Environmental Health, Kita-Kyushu 807-8555, Japan.
Anticancer Res. 2005 Nov-Dec;25(6A):3755-61.
Thymidine phosphorylase (TP) is a key enzyme involved in pyrimidine nucleoside metabolism. Dihydropyrimidine dehydrogenase (DPD) is the major catabolic enzyme of 5-fluorouracil (5-FU). These are important enzymes in the pyrimidine salvage pathway and are considered to be key enzymes for determining the prognosis of patients with gastrointestinal cancer. In the present study, TP and DPD were quantified and evaluated in gastric and colorectal cancer.
In 111 cases of malignancy, including 30 gastric cancers and 81 colorectal cancers, the expression levels of both TP and DPD in fresh-frozen samples from either tumor or adjacent normal tissue were quantified using enzyme-linked immunosorbent assay (ELISA). The relationships between TP or DPD expression levels in tumor tissues or adjacent normal tissues and clinicopathological factors were evaluated.
The TP expression levels in gastric or colorectal tumor tissues were found to be significantly higher than those in the adjacent normal tissue. Although the DPD expression levels in gastric tumor tissue were significantly higher than those in adjacent normal tissue, the DPD expression levels in colorectal tumor tissue were nearly identical to those in the adjacent normal tissue. The DPD expression levels in gastric tumor tissues were significantly higher than those in colorectal tumor tissues. The TP expression levels correlated significantly with the DPD expression levels in tumor or adjacent normal tissues. The DPD expression levels in tumor tissues significantly correlated with those in adjacent normal tissue.
The difference in DPD expressions between gastric and colorectal cancer tissues may reflect the organ specificity of the carcinomas and a difference in chemotherapeutic sensitivity to 5-FU or its analogs. The correlation between TP and DPD expression levels suggests the existence of a common regulatory pathway.
胸苷磷酸化酶（TP）是嘧啶核苷代谢中的关键酶。二氢嘧啶脱氢酶（DPD）是5-氟尿嘧啶（5-FU）的主要分解代谢酶。这些是嘧啶补救途径中的重要酶，被认为是决定胃肠道癌患者预后的关键酶。在本研究中，对胃癌和结直肠癌中的TP和DPD进行了定量和评估。
在111例恶性肿瘤患者中，包括30例胃癌和81例结直肠癌，使用酶联免疫吸附测定（ELISA）对肿瘤或邻近正常组织的新鲜冷冻样本中TP和DPD的表达水平进行定量。评估肿瘤组织或邻近正常组织中TP或DPD表达水平与临床病理因素之间的关系。
发现胃癌或结直肠癌组织中的TP表达水平显著高于邻近正常组织。虽然胃癌组织中的DPD表达水平显著高于邻近正常组织，但结直肠癌组织中的DPD表达水平与邻近正常组织几乎相同。胃癌组织中的DPD表达水平显著高于结直肠癌组织。肿瘤或邻近正常组织中的TP表达水平与DPD表达水平显著相关。肿瘤组织中的DPD表达水平与邻近正常组织中的DPD表达水平显著相关。
胃癌和结直肠癌组织中DPD表达的差异可能反映了癌症的器官特异性以及对5-FU或其类似物化疗敏感性的差异。TP和DPD表达水平之间的相关性表明存在共同的调节途径。
