根据ERCC1、RRM1及TUBB3检测结果对食管鳞癌患者实行个体化辅助治疗的随机对照研究

Personalized adjuvant therapy for esophageal squamous carcinoma according to ERCC1,RRM1 and TUBB3:A randomized and controlled study

目的:对食管鳞癌患者根据切除修复交叉互补基因1(ERCC1)、核糖核酸还原酶基因1(RRM1)及人微管蛋白β3基因(TUBB3)mRNA在食管鳞癌组织中的表达水平选择敏感药物进行辅助化疗,评估该个体化辅助治疗方案对食管鳞癌患者预后的影响。方法:选取2011年8月-2012年8月于本院接受食管癌根治术的患者240例,病理证实均为鳞癌,分期为Ⅲa-Ⅲc期。将入组患者随机分为两组:对照组120例,采用顺铂(DDP)联合氟尿嘧啶(5-FU)方案进行辅助化疗;研究组120例,采用荧光定量聚合酶链反应法(FQPCR)对120例食管鳞癌患者肿瘤组织中ERCC1、RRM1及TUBB3 mRNA表达水平进行检测,并根据三种基因mRNA表达水平选取DDP、吉西他滨(GEM)和多西他赛(DOC)等药物进行辅助化疗。对以上入组患者进行为期1年的随访,比较两组患者治疗的中位疾病进展时间(mTTP)和1年疾病复发率。结果:至随访结束,对照组和研究组分别收集数据110例和114例。对照组和研究组mTTP分别为7.3个月和10.5个月(P<0.001)。ERCC1、RRM1及TUBB3三种基因mRNA均为高表达的患者1年内疾病复发率显著高于其他基因型组,三种基因同时高表达为疾病复发的独立危险因素(OR=2.128,P=0.039,95%CI=1.039-4.359)。结论:根据ERCC1、RRM1及TUBB3检测结果选择敏感化疗药物对食管鳞癌患者实行个体化治疗可以使患者有较大的获益,以上三种基因同时高表达是Ⅲ期食管癌复发的独立危险因素。

Objective：To explore the effect of personalized chemotherapy according to the level of ERCC1 ,RRM1 and TUBB3 in esophageal squamous carcinoma. Methods：Selected 240 patients who accepted radical resection of e- sophageal carcinoma from August 2011 to August 2012 in our hospital, all of the tumors were proved to be esophageal squamous carcinoma by pathology, and the stages were m a - Hi c according to the TNM staging. The patients were di- vided to control group and treatment group, the former were given DDP combined 5 - FU, and the latter were given one of the different chemotherapy drugs of DDP, GEM and DOC according to the detection results of ERCC1, RRM1 and TUBB3. After 1 - year follow up compared the mT＇FP and recurrence rate of the two groups. Results： At the end of the study we collected data of 110 and 114 cases in control group and treatment group, respectively. Statistics difference of mTTP were observed in control group and treatment group （7.3 vs 10.5 months,P 〈0. 001 ）. There were some pa- tients in which the ERCC1,RRM1 and TUBB3 were all over expressing. The 1 -year recurrence rate of these cases, which was much higher than other cases （ P 〈 0.001 ）. The high expression of all these three genes was the independ- ent risk factor of esophageal carcinoma （ OR = 2. 128, P = 0.039,95 % CI = 1. 039 - 4. 359 ）. Conclusion ： Patients di- agnosed with esophageal carcinoma of 111 a - Ill c stages could benefit from the personalized chemotherapy according to the level of ERCC1, RRM1 and TUBB3 in esophageal squamous carcinoma, the high expression of all above genes re- lated to the recurrence of HI stage disease.