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胸苷酸合成酶和二氢嘧啶脱氢酶 mRNA 在肝内胆管癌中的作用。

Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA in intrahepatic cholangiocarcinoma.

机构信息

Department of Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.

出版信息

Surg Today. 2012 Jan;42(2):135-40. doi: 10.1007/s00595-011-0054-z. Epub 2011 Dec 6.

Abstract

PURPOSE

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil and possible predictive markers. We conducted this study to clarify if TS and DPD gene expressions are a prognostic indicator for intrahepatic cholangiocarcinoma (IHCC).

METHODS

The subjects of this study were 21 patients with IHCC who had undergone surgical resection. Intratumoral TS and DPD mRNA expressions were examined using the Danenberg tumor profile method and classified into two groups according to the median value of each. We then compared the clinicopathological variables, including prognosis, between the high and low expression groups.

RESULTS

Low DPD expression was correlated with macroscopic type, namely, mass-forming + infiltrative (P = 0.08). Postoperative survival rates in the low DPD expression group were significantly lower than those in the high DPD expression group. Multivariate analysis revealed macroscopic type to be an independent prognostic factor, whereas TS mRNA expression did not correlate with any clinicopathological variables, including prognosis.

CONCLUSIONS

Low DPD mRNA expression was related to macroscopic type and associated with poor prognosis. DPD mRNA expression in tumor cells is suggested to be an important regulator of malignant behavior in IHCC.

摘要

目的

胸苷酸合成酶(TS)和二氢嘧啶脱氢酶(DPD)是 5-氟尿嘧啶代谢中的重要酶,也是可能的预测标志物。本研究旨在阐明 TS 和 DPD 基因表达是否是肝内胆管癌(IHCC)的预后指标。

方法

本研究的对象是 21 例接受手术切除的 IHCC 患者。采用 Danenberg 肿瘤谱法检测肿瘤内 TS 和 DPD mRNA 表达,并根据每种基因的中位数将其分为两组。然后比较高、低表达组的临床病理变量,包括预后。

结果

低 DPD 表达与大体类型有关,即肿块形成+浸润型(P = 0.08)。低 DPD 表达组的术后生存率明显低于高 DPD 表达组。多因素分析显示,大体类型是独立的预后因素,而 TS mRNA 表达与包括预后在内的任何临床病理变量均无关。

结论

低 DPD mRNA 表达与大体类型有关,与预后不良相关。肿瘤细胞中的 DPD mRNA 表达可能是 IHCC 恶性行为的重要调节因子。

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