ERCC1、TYMS和TUBB3 mRNA表达对HER-2阴性晚期胃癌化疗疗效的影响

Influences of ERCC1,TYMS,TUBB3 mRNA expressions on chemotherapeutic efficacy in patients with HER2-negative advanced gastric cancer

目的探讨切除修复交叉互补基因1(ERCC1)、胸苷酸合酶(TYMS)和β-微管蛋白Ⅲ(TUBB3)多基因联合检测对人类表皮生长因子受体-2(HER-2)阴性晚期胃癌个体化化疗疗效及预后的影响。方法将96例HER-2阴性晚期胃癌患者随机分为两组,各48例。对照组采用DCX(多西紫杉醇75 mg/m2d1;顺铂75 mg/m2d1;卡培他滨1 000 mg/m2,2次/d,d1~14)方案;试验组进行ERCC1、TYMS和TUBB3的m RNA表达水平的检测,并根据结果针对性地选择DCX方案、DX方案和FOLFOX4方案。观察两组患者的生活质量、副反应、化疗有效率、疾病进展时间(TTP)和总生存时间(OS)。结果对照组生活质量改善率、TTP和OS均低于试验组(P<0.05或P<0.01);两组骨髓抑制率、肝肾损害率无统计学差异(P>0.05)。在化疗缓解率(48.3%vs 10.5%,P<0.05)、中位TTP(8.5个月vs 4.6个月)和中位OS(15.4个月vs 8.8个月)方面,试验组TUBB3、TYMS、ERCC1中有0或1个基因高表达的患者均优于有2或3个基因高表达患者(P均<0.01)。结论依据ERCC1、TYMS和TUBB3基因联合检测指导HER-2阴性晚期胃癌患者化疗方案的选择,可提高疗效、改善患者生活质量、延长生存期。三者检测在HER-2阴性晚期胃癌个体化治疗中的预测价值,尚待大样本、细分的随机对照临床研究进一步证实。

Objective To investigate the impacts of excision repair cross complementation group 1 （ERCC1） ,thymidylate synthase （TYMS）,β-tubulin-Ⅲ （TUBB3） mRNA expressions on individualized chemotherapy and prognosis of patients with human epidermal growth factor receptor （HER）-2 negative advanced gastric cancer, Methods A total of 96 Her2- negative gastric cancer patients were randomly divided into control group and test group （ n = 48, each）. DCX regimen （docctaxel 75 mg/m^2 d1 ;cisplatin 75 mg/m^2 d1 ;capecitabine 1 000 mg/m^2 ,2/d,d1-14 ） was performed in control group. In test group,the targeted selection of DCX,DX and FOLFOX4 regimens were determined based on the detection results of ERCC1 ,TYMS,TUBB3 mRNA expressions. The quality of life, side effects, chemotherapy efficiency, time to progression （TTP） and overall survival（OS） were observed between two groups. Results The improvement rate of quality of life ,TTP and OS in control group were significantly lower than those in test group（ P 〈 0. 05, P 〈 0. 01 ）. There were no significant differences in the incidence of myelosuppression, liver and kidney damage between two groups （ all P 〉 0.05 ）. In test group,the remission rate of chemotherapy （48.3% vs 10. 5% , P 〈 0.05 ） , median TI＇P（ 8.5 months vs 4.6 months） and OS （ 15.4 months vs 8.8 months） in patients with 0 or 1 gene high expressions of TUBB3 ,TYMS and ERCC1 were superior to the patients with 2 or 3 gene high expressions （ all P 〈 0.01 ）. Conclusions According to the combined detection of ERCC1 ,TYMS and TUBB3 gene,the choice of chemotherapy regimens in treatment for HER-2 negative advanced gastric cancer can improve the effect of chemotherapy, improve the quality of life and prolong the survival time of patients. The predictive value of ERCC1, TYMS and TUBB3 gene detection in individualized treatment of HER-2 negative advanced gastric cancer remains to be further confirmed by a randomized controlled clinical study of large sample and subdivision.