Higher expression of deoxyuridine triphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer.
Higher expression of deoxyuridine triphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer.
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DOI：
10.1136/jcp.2008.060004
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发表时间：
2009-04
影响因子：
3.4
通讯作者：
Kage M
中科院分区：
文献类型：
--
作者：
Kawahara A;Akagi Y;Hattori S;Mizobe T;Shirouzu K;Ono M;Yanagawa T;Kuwano M;Kage M
5-氟尿嘧啶（5-FU）是最广泛使用的抗癌药物之一；然而，5-FU 的活性是由限制其激活或降解的几种酶的存在决定的，这些酶包括二氢嘧啶脱氢酶 (DPD)、乳清酸磷酸核糖基转移酶 (OPRT)、胸苷酸合酶 (TS)、胸苷激酶 (TK)、胸苷磷酸化酶 (TP) 和脱氧尿苷三磷酸酶 (dUTPase)。本研究的目的是比较有和没有远处转移的原发性结直肠癌患者中这些酶的表达水平。此外，对原发肿瘤和相应转移瘤之间的这些表达水平进行了比较。 55例结直肠癌患者中，20例无转移，35例发生远处转移。通过免疫组织化学，强表达被分类为阳性，而弱至中度或无表达被分类为阴性。在六种5-FU相关酶中，原发肿瘤转移患者与原发肿瘤转移患者中，表达dUTPase（54% vs 15%；p = 0.005）、TK（26% vs 0%；p = 0.019）和DPD（17% vs 45%；p = 0.033）的患者数量有显着差异。分别为非转移。在35名转移患者中，从原发灶到转移灶，OPRT（34.3%）、TS（40.0%）和dUTPase（42.9%）的表达变化显着更大。相比之下，OPRT、TS 和 dUTPase 的表达分别在 6、5 和 7 名患者的转移部位下降。从结直肠癌中六种 5-FU 相关酶的比较研究来看，原发性肿瘤与其相应的转移性肿瘤之间 dUTPase 的表达差异最为显着。 dUTPase 可能是结直肠癌转移潜力的预测生物标志物。
5-Fluorouracil (5-FU) is one of the most widely used anticancer drugs; however, the activity of 5-FU is determined by the presence of several enzymes that limit its activation or degradation, and these include dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), thymidine kinase (TK), thymidine phosphorylase (TP) and deoxyuridine triphosphatase (dUTPase). The aim of this study was to compare the expression levels of these enzymes between the primary colorectal cancer of patients with and without distant metastases. Furthermore, there was a comparison of these expression levels between the primary tumour and the corresponding metastasis. Of 55 patients with colorectal cancer, 20 had no metastasis and the other 35 had distant metastasis. A strong expression was classified as positive, while weak to moderate or no expression was negative by immunohistochemistry. Of the six 5-FU-related enzymes, the numbers of patients with expression of dUTPase (54% versus 15%; p = 0.005), TK (26% versus 0%; p = 0.019) and DPD (17% versus 45%; p = 0.033) were significantly different in those with primary tumours with metastasis compared with those with non-metastasis, respectively. The altered expression of OPRT (34.3%), TS (40.0%) and dUTPase (42.9%) was significantly greater from primary to metastasis among the 35 patients with metastasis. By contrast, the expression of OPRT, TS and dUTPase was decreased in 6, 5 and 7 patients, respectively, in metastatic sites. From this comparative study of the six 5-FU-related enzymes in colorectal cancer, the expression of dUTPase was most significantly different between primary tumours and their corresponding metastatic tumour. It is suggested that dUTPase may be a predictive biomarker for the metastatic potential of colorectal cancer.
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影响因子：
6.4
作者：
Ichikawa, Wataru;Takahashi, Takehiro;Hirayama, Renzo
通讯作者：
Hirayama, Renzo
影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
4.4
作者：
Wei, XX;Elizondo, G;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
影响因子：
8.4
作者：
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通讯作者：
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