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Received:April 07, 2019 Published Online:December 20, 2019
Received:April 07, 2019 Published Online:December 20, 2019
中文摘要: 目的 探讨二氢嘧啶脱氢酶(DPD)、胸苷酸合成酶(TS)蛋白表达与氟尿嘧啶类药新辅助化疗胃癌患者临床病理资料、化疗近期疗效及预后的关系。方法 选择中国医科大学附属第一医院胃肠肿瘤外科2011年7月至2015年10月收治的50例新辅助化疗胃癌患者为研究对象,术前给予氟尿嘧啶类药联合奥沙利铂或多西紫杉醇方案进行化疗。分别于化疗前和化疗两周期行血液学检查，采用免疫组化法检测患者DPD、TS蛋白表达水平,分析其与疗效和预后的关系。结果 胃癌组织中DPD阳性表达率为52.0%,TS阳性表达率为48.0%。DPD阳性表达在不同年龄、性别、肿瘤大小、Borromann分型、组织分型、T分期、N分期差异均无统计学意义(P>0.05)。TS阴性表达率在不同年龄、性别、肿瘤大小、Borromann分型、组织分型、N分期差异无统计学意义(P>0.05),不同T分期TS蛋白阳性表达率有统计学差异(P<0.05)。DPD蛋白阳性表达组化疗有效率(76.9%)显著高于DPD蛋白阴性表达组(25.0%，P<0.01),TS蛋白阳性表达组化疗有效率(58.3%)与TS蛋白阴性表达组有效率(46.2%)无统计学差异（P>0.05）。化疗前后血液学指标差异显示WBC、PLT、CA199指标均出现显著性下降(P<0.01),而HGB、CEA、APF无显著性差异(P>0.05)。DPD阳性表达组患者3年生存率为65.5%,显著高于DPD阴性表达组3年生存率(45.9%，P<0.05)；TS阴性表达组患者3年总生存率为65.4%,显著高于TS阳性表达组3年生存率(41.7%，P<0.05)。结论 DPD蛋白可作为局部进展期胃癌氟尿嘧啶类药联合化疗疗效的预测指标,且能指导预后,TS蛋白亦能作为预后指导。
中文关键词: 胃癌 二氢嘧啶脱氢酶 胸苷酸合成酶 新辅助化疗；氟尿嘧啶
Abstract:Objective To investigate the relationship between the expression of dihydropyrimidine dehydrogenase (DPD),thymidylate synthase (TS) and the clinicopathological data,the short-term effect of chemotherapy and prognosis of gastric cancer patients received fluorouracil based neoadjuvant chemotherapy. Methods A total of 50 gastric cancer patients who received neoadjuvant chemotherapy at First Hospital of China Medical University from July 2011 to October 2015 were selected as study objects.The patients were treated with fluorouracil combined with oxaliplatin or docetaxel before operation.The hematology was examined before and after chemotherapy.The expression level of DPD and TS proteins was detected by immunohistochemistry in each patient,and their relationship with curative effect and prognosis was analyzed. Results The positive rate of DPD and TS was 52.0% and 48.0% in gastric cancer tissues respectively.There was no significant difference of DPD expression in age,gender,tumor size,Borromann type,tissue type,T stage and N stage (all P>0.05).There was no significant difference in the negative expression rate of TS in different age,gender,tumor size,Borromann type,histological type and N stage (all P>0.05).The positive expression rate of TS protein in different T stages was significantly different (P<0.05).The effective rate of chemotherapy in DPD positive expression group was significantly higher than that in DPD negative expression group ［76.9% (20/26) vs 25.0% (6/24),P<0.01］.There was no significant difference in the effective rate of chemotherapy in TS positive expression group and TS negative expression group ［58.3% (14/24) vs 46.2% (12/26),P>0.05］.The hematological indexes before and after chemotherapy showed that WBC,PLT and carbohydrate antigen (CA)-199 decreased significantly (all P<0.01),while globin (HGB),carcinoembryonic antigen (CEA) and alph hemoa fetoprotein (AFP) had no significant difference (all P>0.05).The 3-year survival rate in DPD positive group was significantly higher than that in DPD negative group (65.5% vs 45.9%,P<0.05),and TS negative group was significantly higher than that TS positive group (65.4% vs 41.7%,P<0.05). ConclusionDPD protein can be used as a predictor of the efficacy of fluorouracil combined chemotherapy in locally advanced gastric cancer,and it can also guide the prognosis.TS protein is related to the prognosis of locally advanced gastric cancer.
keywords: Gastric cancer Dihydropyimidine dehydrogenase Thymidylate synthase Neoadjuvant chemotherapy Fluorouracil
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基金项目:辽宁省自然科学基金(20180530026)
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