5-FU相关代谢酶表达与胃癌化疗敏感性的关系

摘要

目的:比较新辅助介入化疗前后胃癌组织内胸腺嘧啶合成酶(thymidylate synthase,TS),二氢嘧啶脱氢酶(dihydropymidine dehydrogenase,DPD),胸腺嘧啶磷酸化酶(thymidine phosphorylase,TP),亚甲基四氢Ⅱ十酸还原酶(methylenetetrahydrofolate reductase,MTHFR)等5-FU相关代谢酶表达,探讨其与化疗疗效的相关性.方法:对49例进展期胃癌患者随机分为新辅助化疗手术组(39例)和直接手术组(10例),对胃镜活检及手术后组织标本行实时定量PCR检测其中TS、DPD、TP和MTHFR的表达.结果:新辅助化疗组分为:化疗有效组(27)例和无效组(12例),有效率69.2％；化疗前有效组4种基因的表达水平与无效组相比均低,其中DPD差异较明显(P＜0.05)；化疗后有效组TS、TP、DPD表达较无效组低50.3％、51.3％和31.2％(P＜0.05)；有效组TS和TP较化疗前分别下降38.6％和48.7％(P＜ 0.05),而无效组则前后变化不明显(P＞0.05).结论:介入化疗前肿瘤内DPD表达或者介入后TS、TP、DPD表达以及介入前后TS和TP表达变化程度与化疗敏感性相关.%Objective: To compare the pre- and post-neoadjuvant intervention chemotherapeutic expression levels of thymidylate synthase(TS) .dihydropymidine dehydrogenase(DPD),thymidine phosphorylase(TP) ,and methylenetetrahydrofolate reductase (MTH FR), and to explore the relationship between the expression of these four genes and the neoadjuvant intervention chemotherapeutic effects. Methods:Forty-nigh patients with advanced gastric cancer were divided into neoadjuvant chemotherapeutic group (39 pa tients) and operative group (10 patients). The gene expression levels of TS,TP,DPD,and MTHFR in biopsy specimens from gastro-scope and tumor tissue specimens after surgical resection were detected by real-time PCR. Results; According to the results of histopathology, neoadjuvant chemotherapeutic patients were divided into chemotherapeutic effective group (27 cases) and noneffective group (12 cases). The effective rate of neoadjuvant chemotherapy was 69.2%. The expression levels of four detected genes in the tu mors of effective patients before neoadjuvant intervention chemotherapy were generally lower than that of the noneffective cases,and the level of DPD decreased 5.2%(P < 0.05). After neoadjuvant intervention chemotherapy,the levels of TS,TP and DPD in the ef fective group were 50.3%, 51.3%, and 31.2% lower than those of noneffective group, respectively all P < 0.05). The expression levels of TS and TP in effective group decreased by 38.6% and 48.7% compared with that before chemotherapy, respectively (P < 0.05), while the levels of four genes in noneffective group exhibited no significant difference between before and after chemotherapy (P > 0.05). Conclusion: The patients with low level of DPD expression in tumors before neoadjuvant chemotherapy and low levels of TS, TP,DPD after neoadjuvant chemotherapy were sensitive to the neoadjuvant intervention chemotherapy. And the decreased levels of TS and TP after neoadjuvant chemotherapy were important for evaluating the prognosis of neoadjuvant chemotherapy.