CAJ | 학술논문

目的分析进展期胃癌患者新辅助化疗应用SOX方案后肿瘤组织标本氟尿嘧啶代谢因子水平变化与临床疗效的相关性.方法回顾性分析2012年6月至2013年3月解放军总医院普通外科收治的32例胃癌患者临床资料,其中,男23例、女9例,年龄56.6(40～75)岁.治疗前分期评估均为第7版美国肿瘤联合会(AJCC)Ⅱ～Ⅲ期.给予口服氟尿嘧啶(替吉奥胶囊80 mg·m-2·d-1,第1～14天)联合奥沙利铂(130 mg/m2,静脉滴注,第1天)新辅助化疗后进行外科手术切除,术中取得新鲜肿瘤及正常组织标本,应用实时反转录(RT)-PCR技术对氟尿嘧啶代谢因子胸腺嘧啶磷酸化酶(TP)、胸腺嘧啶合成酶(TS)、二氢嘧啶脱氢酶(DPD)、乳清酸磷酸核糖转移酶(OPRT)的表达水平进行检测,分析其与化疗效果的相关性.结果 32例患者均完成了至少2个周期新辅助化疗,21例患者肿瘤达临床缓解,有效率为65.6％(21/32).10例患者肿瘤达组织学缓解,反应率为31.3％ (10/32).RT-PCR检测结果显示:临床缓解胃癌患者组织中OPRT mRNA表达水平高于未缓解者(3.95±0.81比1.79±0.64,P=0.005);弥漫型胃癌患者(n=22)胃癌组织中OPRT mRNA表达显着高于肠型胃癌(n=10)患者(2.54±0.75比1.49±0.56,P=0.014).有淋巴结转移患者(n=13)胃癌组织中TS、TP mRNA表达均高于无淋巴结转移(n=19)者(均P＜0.05).而DPD mRNA各组表达差异均无统计学意义(均P＞0.05).结论肿瘤组织中OPRT mRNA表达水平与新辅助化疗疗效相关,TS、TP表达水平与新辅助化疗后淋巴结转移相关.OPRT、TS和TP将有可能成为进展期胃癌以氟尿嘧啶药物为基础新辅助化疗方案的有效性预测因子.
목적 분석진전기위암환자신보조화료응용SOX방안후종류조직표본불뇨밀정대사인자수평변화여림상료효적상관성.방법 회고성분석2012년6월지2013년3월해방군총의원보통외과수치적32례위암환자림상자료,기중,남23례、녀9례,년령56.6(40～75)세.치료전분기평고균위제7판미국종류연합회(AJCC)Ⅱ～Ⅲ기.급여구복불뇨밀정(체길오효낭80 mg·m-2·d-1,제1～14천)연합오사리박(130 mg/m2,정맥적주,제1천)신보조화료후진행외과수술절제,술중취득신선종류급정상조직표본,응용실시반전록(RT)-PCR기술대불뇨밀정대사인자흉선밀정린산화매(TP)、흉선밀정합성매(TS)、이경밀정탈경매(DPD)、유청산린산핵당전이매(OPRT)적표체수평진행검측,분석기여화료효과적상관성.결과 32례환자균완성료지소2개주기신보조화료,21례환자종류체림상완해,유효솔위65.6％(21/32).10례환자종류체조직학완해,반응솔위31.3％ (10/32).RT-PCR검측결과현시:림상완해위암환자조직중OPRT mRNA표체수평고우미완해자(3.95±0.81비1.79±0.64,P=0.005);미만형위암환자(n=22)위암조직중OPRT mRNA표체현착고우장형위암(n=10)환자(2.54±0.75비1.49±0.56,P=0.014).유림파결전이환자(n=13)위암조직중TS、TP mRNA표체균고우무림파결전이(n=19)자(균P＜0.05).이DPD mRNA각조표체차이균무통계학의의(균P＞0.05).결론 종류조직중OPRT mRNA표체수평여신보조화료료효상관,TS、TP표체수평여신보조화료후림파결전이상관.OPRT、TS화TP장유가능성위진전기위암이불뇨밀정약물위기출신보조화료방안적유효성예측인자.
Objective To analyze the impact of mRNA expression of oral fluoropyrimidine (S-1) metabolism on treatment outcomes in locally advanced gastric cancer patients on preoperative S-1 oxaliplatinbased chemotherapy.Methods Between June 2012 and March 2013,32 patients with preoperative AJCC stage Ⅱ-Ⅲ gastric cancer patients were enrolled.They received S-1 (80 mg · m-2 · d-1,days 1-14) and oxaliplatin (130 mg/m2,day 1) every 3 weeks and subsequently underwent gastrectomy with D2 lymphadenectomy.Paired tumor and normal fresh frozen tissues were collected to evaluate the mRNA levels of thymidylate synthase (TS),thymidine phosphorylase (TP),dihydropyrimidine dehydrogenase (DPD) and OPRT with quantitative reverse transcription(RT)-PCR.Results Among them,21 (65.6％) patients had clinical tumor response and histological response occurred in 10 (31.3％) patients.Quantitative RT-PCR results showed that OPRT mRNA expression was significantly higher in clinical tumor responders than nonresponders (3.95 ± 0.81 vs 1.79 ± 0.64,P =0.005).Diffuse-type gastric cancer patients (n =22)demonstrated higher OPRT expression levels than intestinal-type (n =10) ones (2.54 ± 0.75 vs 1.49 ±0.56,P=0.014).The mRNA expressions of TS and TP in gastric cancer tissues with lymph node (LN)metastasis(n =13) were significantly higher than those in gastric cancer tissues without LN metastasis(n =19,both P ＜ 0.05).Similar results were not found for comparing dihydropyrimidine dehydrogenase expression levels(all P ＞ 0.05).Conclusion OPRT,TS and TP may become potential predictive biomarkers in advanced gastric cancer patients on oral fluoropyrimidine (S-1)-based chemotherapy.