氟尿嘧啶代谢酶在胃癌组织中表达与替吉奥化疗疗效相关性的Meta分析

发布时间：2018-07-23 14:30

【摘要】：目的：目前氟尿嘧啶代谢酶表达水平对替吉奥治疗胃癌的疗效预测价值还存在争议,本次Meta分析目的为研究氟尿嘧啶代谢酶在胃癌组织中的表达水平与替吉奥治疗胃癌疗效的相关性,包括对胸苷酸合成酶(thymidylate synthase, TS)、胸苷磷酸化酶(thymidine phosphorylase, TP)、乳清磷酸核糖基转移酶(orotate phosphoribosyl transferase, OPRT)和二氢嘧啶脱氢酶(dihydropyrimidine dehydrogenase, DPD)表达水平的研究,并进一步探讨胃癌组织中氟尿嘧啶代谢酶表达作为替吉奥疗效指标的意义。方法：制定检索策略及文献的纳入和排除标准,计算机检索PubMed和Embase databases英文数据库以及中国生物医学文献统计库(CBM)、相关期刊论文(CNKI)、中文科技期刊数据库(VIP)等中文数据库,并检索所获的文献的参考文献及重要会议资料,纳入对使用替吉奥治疗的胃癌患者癌组织中的氟尿嘧啶代谢酶进行测定与临床疗效观察的研究(最后检索日期2015.4.19)。采用Stata/SE 12.0和Cochrane协作网Review Manager5.3进行统计分析。结果：本文最终纳入10个临床研究,包含555例患者。Meta分析结果显示,9篇文献有近期疗效的数据,TS高表达或阳性(high/+)为159例,TS低表达或阴性(low/-)为186例,TP (high/+)为116例,TP (low/-)为125例,OPRT (high/+)为179例,OPRT (low/-)为107例,DPD (high/+)为155例,DPD (low/-)为186例,其中OPRT (high/+)患者与OPRT (low/-)患者的客观缓解率有显著差异(48.6%vs10.3%,合并OR值为8.06,95%置信区间4.06-16.02,P0.001),DPD (high/+)患者的客观缓解率显著高于DPD (low/-)患者(42.6%vs30.6%,合并OR值为1.95,95%置信区间1.21-3.13,P=0.006),而胃癌患者的客观缓解率在TP、TS的表达水平之间不存在显著差异。4篇文献有中位生存期的数据,其中TS (high/+)为50例,TS (low/-)为97例,TP (high/+)为51例,TP (low/-)为56例,OPRT (high/+)为81例,OPRT (low/-)为23例,DPD (high/+)为47例,DPD (low/-)为131例。虽然TP (low/-)、TS (low/-)及DPD (high/+)组有较高的中位总生存期,但结果没有显著差异。OPRT (high/+)组的中位总生存期是OPRT (low/-)组的1.19倍,差异具有统计学意义(p=0.076)。结论：胃癌组织中OPRT (high/+)、DPD (high/+)的患者,经替吉奥治疗后,客观缓解率较高。OPRT (high/+)的患者有更长的中位总生存期。胃癌组织中OPRT及DPD的表达水平可以作为替吉奥疗效的预测指标。
[Abstract]:Objective: at present, the expression of fluorouracil metabolic enzymes in the treatment of gastric cancer is still controversial. The purpose of this Meta analysis was to investigate the relationship between the expression of fluorouracil metabolase in gastric cancer and the therapeutic effect of tiguor on gastric cancer. Including the expression of thymidine synthase (thymidylate synthase, TS), thymidine phosphorylase (thymidine phosphorylase, TP), whey phosphate ribonyltransferase (orotate phosphoribosyl transferase, OPRT) and dihydropyrimidine dehydrogenase (Dihydropyrimidine dehydrogenase) (dihydropyrimidine dehydrogenase, DPD), To explore the significance of fluorouracil metabolic enzyme expression in gastric cancer as a therapeutic index of teguir. Methods: the retrieval strategy and the inclusion and exclusion criteria of literature were established. The Chinese databases such as PubMed and Embase databases English databases and (CBM), Chinese journal full-text database (CNKI), Chinese sci-tech periodicals database (VIP) were searched by computer. The references and important conference data were retrieved to study the determination of fluorouracil metabolase in cancer tissues of patients with gastric cancer treated with tegeot and the observation of clinical efficacy (last search date: April 19, 2015). Stata/SE 12.0 and Cochrane Review Manager5.3 were used for statistical analysis. Results: 10 clinical studies were included in this article. Results of Meta-analysis of 555 patients. Meta-analysis showed that the data of TS overexpression or positive (high/) in 9 articles were 159cases with low expression or negative (lowr-), 186cases with TP (high/), 116cases with TP (low-), 125cases with OPRT (high/), 179cases with OPRT (lowr-), 107cases with OPRT (lowr-). DPD (high/) in 155 cases of DPD (low-) was 186 cases. There was a significant difference in objective remission rate between OPRT (high/) patients and OPRT (low-) patients (48.6 vs 10.3, OR = 8.06 卤95% CI 4.06-16.02P0.001). The objective remission rate of high/ patients was significantly higher than that of DPD patients (42.6 vs 30.6, OR = 1.9595% confidence interval 1.21-3.13P0.006), while that of patients with gastric cancer was higher than that of DPD patients (42.6vs30.6and OR = 1.9595% confidence interval 1.21-3.13P0.006), while that of high/ patients was significantly higher than that of DPD (lowr-) patients (42.6vs30.6A = 1.9595% CI = 1.21-3.13P0.006). There was no significant difference in the expression level of TPTs between the two groups. 4 articles had median survival time data. TS (high/) was 50 cases of TS (low / -) 97 cases of TP (high/) 51 cases of TP (low-) 56 cases of OPRT (high/) 81 cases of OPRT (low-) 23 cases of DPD (high/) 47 cases of DPD (r-low-) 131 cases. Although the median total survival time of TP (lowr-) TS and DPD (high/) group was higher, there was no significant difference. The median total survival time of high/ group was 1.19 times that of OPRT group, and the difference was statistically significant (p0. 076). Conclusion: the patients with OPRT (high/) and DPD (high/) in gastric cancer have a longer median total survival time after tigor treatment. The objective remission rate of high/ is higher. The expression of OPRT and DPD in gastric cancer can be used as a predictor of tigor's curative effect.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.2

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