TS、DPD、TP和OPRT基因表达在预测胃癌患者治疗效果中的价值  

Expressions of genes thymidylate synthase and dihydropyrimidine dehydrogenase as biomarkers in predicting treatment effects of gastric cancer

作　　者：王芳[1] 年亮 戴光荣[1] 薛顺和 WANG Fang;NIAN Liang;DAI Guang-rong;XUE Shun-he(Department of Gastroenterology,Affiliated Hospital of Yan＇an University Yanan City,Yan＇an 716000,China)

机构地区：[1]延安大学附属医院消化内科,陕西延安716000

出　　处：《中国中西医结合消化杂志》2018年第8期649-656,共8页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：延安市科技创新团队"延安市胃癌高发区胃癌筛查和干预创新团队"(No:2016CXTD-05)

摘　　要：[目的]本实验通过分析胃癌病例样本中胸苷酸合酶(TS)、二氢嘧啶脱氢酶(DPD)、胸苷酸磷酸化酶(TP)和乳清酸磷酸核糖基转移酶(OPRT)基因的表达情况,鉴定了这些基因作为生物标志物在S-1制剂辅助参与的胃癌治疗中的作用。[方法]符合纳入标准并且采样结果可纳入分析的病例共计274例。所有病例样本均进行甲醛浸泡并切片观察和保存,显微切割肿瘤样本后进行RT-PCR以检测TS,DPD,TP和OPRT基因表达,并根据看家基因β-肌动蛋白表达量进行量化比较。对每个基因的表达量以25%,50%和75%进行表达量高低的分组。[结果]在根据TS表达量高低进行的分组中,在S-1治疗组和仅手术治疗组的对比结果显示,在TS高表达量组(≥75%,HR=0.35,95%CI0.21~0.61)中患者生存风险比(HR)显著低于(P=0.01)TS低表达量组(<75%,HR=0.74,95%CI0.56~1.01)。根据DPD表达量进行的分组中与TS表达组检测结果类似,S-1治疗可显著降低DPD高表达组的HR。但在TP和OPRT表达组中并未发现类似结果,且患者生存情况与TP和OPRT表达量亦无相关性。[结论]本研究显示S-1辅助手术治疗对于胃癌患者预后效果更好;基因TS和DPD高表达与S-1辅助治疗的良好预后存在相关性,但基因TP和OPRT的表达与S-1治疗没有关联。[Objective]In the present study,expressions of genes encoded pyrimidine metabolism including thymidylate synthase（TS）,dihydropyrimidine dehydrogenase（DPD）,thymidine phosphorylase（TP）and orotate hosphoribosyltransferase（OPRT）in the gastric cancer samples of patients were tested and analyzed for their potential as biomarkers in the S-1 treatment for gastric cancer.[Methods]A total of 274 patients qualified the inclusion criteria and the results of the analysis were included in the analysis.All specimens from patients were observed and kept as formalin-fixed and paraffin-embedded slides.Gene expressions of TS,DPD,TP and OPRT were measured by RT-PCR withβ-actin used as reference gene.Samples were taken by microdissection from tumor specimens.Patient-cases were categoried by the expression level（low 25%,medium 50% and high 75%）of each gene.[Results]Comparing to the surgury-only patient group,the hazard ratio（HR）of overall survival of S-1 treated patients in the high-TS expression category（≥75%,HR=0.35,95%CI 0.21-0.61）was significantly higher（P=0.01）than that of the low-TS expression category（75%,HR=0.74,95%CI 0.56-1.01）.Similar results showed in the DPD gene expression categories,which indicated S-1 treatment after surgery significantly decreased the HR of high-DPD expres-sion category.However,in the TP and OPRT expressions,no significant differences on HR were found between categories,and the overall survival of patients showed no significant interactions to the expressions of TP and OPRT.[Conclusion]The present study suggests that S-1 treatment after surgery has better overall survival than surgery only.The high expressions of genes TS and DPD in the gastric cancer are associated with the postoperative adjuvant of S-1 treatment after surgery,while TP and OPRT are not relevant.

关 键 词：胃部肿瘤 胸苷酸合酶 二氢嘧啶脱氢酶 生物标志物 化疗 

分 类 号：R735.2[医药卫生—肿瘤]