晚期胃癌患者血清TS、TP表达水平与氟尿嘧啶为基础的化疗疗效及预后的相关性

doi:10.3969/j.issn.1007-3969.2013.04.009

中国癌症杂志 ›› 2013, Vol. 23 ›› Issue (4): 292-297.doi: 10.3969/j.issn.1007-3969.2013.04.009

晚期胃癌患者血清TS、TP表达水平与氟尿嘧啶为基础的化疗疗效及预后的相关性

何琼,高静,王婷婷,陆明,沈琳

北京大学肿瘤医院暨北京市肿瘤防治研究所消化肿瘤内科，恶性肿瘤发病机制及转化研究教育部重点实验室，北京 100142

出版日期:2013-04-25 发布日期:2014-11-19
通信作者: 沈琳　E-mail:lin100@medmail.com.cn

Correlations between serum levels of TS, TP and clinical outcome in Chinese patients with advanced gastric cancer receiving fluorouracil-based chemotherapy

HE Qiong, GAO Jing, WANG Ting-ting, LU Ming, SHEN Lin

Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education; Department of GI Oncology, Peking University Cancer Hospital & Institute, Beijing 100142,China

Published:2013-04-25 Online:2014-11-19
Contact: SHEN Lin E-mail: lin100@medmail.com.cn

摘要/Abstract

摘要：

背景与目的：胸苷酸合成酶(thymidylate synthetase，TS)和胸苷酸磷酸化酶(thymidine phosphorylase，TP)是氟尿嘧啶类药物在体内代谢的关键酶，与胃癌患者接受氟尿嘧啶药物化疗疗效和预后密切相关。本研究旨在探讨晚期胃癌患者血清中TS、TP表达水平与氟尿嘧啶为基础的化疗疗效及预后的相关性。方法：收集2006年1月—2008年10月于北京大学肿瘤医院消化肿瘤内科治疗的109例一线接受氟尿嘧啶类药物为基础化疗的晚期胃癌患者化疗前的血清标本，运用酶联免疫吸附试验(ELISA)方法检测血清中TS、TP表达水平，分析TS、TP表达水平与化疗疗效及患者预后的相关性。结果：近端胃癌患者的TS表达水平高于远端胃癌患者(P=0.035)，腹膜转移患者的TP表达水平明显低于无腹膜转移患者(P<0.001)。TS高表达患者临床获益率(clinical benefit rate，CBR)高于低表达患者(68.75% vs 47.1%，P=0.029)，与患者生存无明显相关。TP高表达患者的中位无进展生存期(progression-free survival，PFS)与总生存期(overall survival，OS)均长于低表达患者(PFS：177 d vs 113 d，P=0.018；OS：399 d vs 234 d，P=0.227)。联合分析TS、TP表达发现，TS低表达且TP高表达患者的中位PFS和OS明显长于TS、TP均低表达患者(PFS：182 d vs 87 d，P=0.042;OS：429 d vs 223 d，P=0.019)。Cox多因素生存分析表明，在TS低表达时，TP表达水平是预后的独立影响因素(HR=1.913，95%CI：1.027~3.564，P=0.041)。结论：在接受氟尿嘧啶为基础化疗的晚期胃癌患者中，TS高表达患者的疗效较好，TP高表达患者的生存期较长，特别是TS低表达且TP高表达患者的生存期明显延长。

关键词: 晚期胃癌, 血清, 胸甘酸合成酶, 胸甘酸磷酸化酶, 氟尿嘧啶

Abstract:

Background and purpose: Thymidylate synthetase (TS) and thymidine phosphorylase (TP) are the key enzymes in metabolism of fluorouracil drugs, and related to the chemotherapy response and prognosis in gastric cancer patients receiving fluorouracil-based chemotherapy. This study aimed to investigate the correlations between serum levels of TS, TP and clinical outcome in Chinese patients with advanced gastric cancer receiving fluorouracilbased chemotherapy. Methods: Serum samples prior to chemotherapy were collected from 109 patients receiving first-line fluorouracil-based chemotherapy in Peking University Cancer Hospital from Jan. 2006 to Oct. 2008. TS and TP levels were analyzed using ELISA assay. Results: TS expressions was higher in patients with proximal gastric cancer than those in patients with distal gastric cancer primary (P=0.035), and TP expression in patients with peritoneal metastasis was significantly lower than those in patients without peritoneal metastasis (P<0.001). Patients with high level of TS had higher clinical benefit rate (CBR) than patients with low level of TS (68.75% vs 47.1%, P=0.029), but no difference was seen between TS levels and survival. The median progression-free survival (PFS) and overall survival (OS) in patients with high level of TP were higher than those in patients with low levels of TP (PFS: 177 d vs 113 d, P=0.018; OS: 399 d vs 234 d, P=0.227). Combined analysis of TS and TP, the results indicated that patients with low TS and high TP levels had significantly longer PFS and OS than patients with low TS and high TP levels (median PFS: 182 d vs 87 d, P=0.042; median OS: 439 d vs 233 d, P=0.019). Cox multivariate regression analysis demonstrated that TP was an independent prognostic factor in patients with low level of TS (HR=1.913, 95% CI: 1.107–3.564, P=0.041). Conclusion: In Chinese patients with advanced gastric cancer receiving first-line fluorouracil-based chemotherapy, patients with high level of TS have a better efficacy and patients with high level of TP have a better prognosis. Especially, patients with TS low and TP high level have the longest PFS or OS.

Key words: Advanced gastric cancer, Serum, Thymidylate synthetase, Thymidine phosphorylase, Fluorouracil

何琼,高静,王婷婷,陆明,沈琳. 晚期胃癌患者血清TS、TP表达水平与氟尿嘧啶为基础的化疗疗效及预后的相关性[J]. 中国癌症杂志, 2013, 23(4): 292-297.

HE Qiong, GAO Jing, WANG Ting-ting, LU Ming, SHEN Lin. Correlations between serum levels of TS, TP and clinical outcome in Chinese patients with advanced gastric cancer receiving fluorouracil-based chemotherapy[J]. China Oncology, 2013, 23(4): 292-297.

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晚期胃癌患者血清TS、TP表达水平与氟尿嘧啶为基础的化疗疗效及预后的相关性

Correlations between serum levels of TS, TP and clinical outcome in Chinese patients with advanced gastric cancer receiving fluorouracil-based chemotherapy

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