TUBB3,TS,ERCC1mRNA表达对晚期胃癌化疗疗效和预后的影响  

Effect of TUBB3, TS and ERCC1 mRNA expression on chemoresponse and clinical outcome of advanced gastric cancer by multiplex branched-DNA liquid chip technology

作　　者：黄进[1] 胡华斌[2] 谢阳春[1] 唐友红[1] 刘巍[1] 钟美佐[1] 

机构地区：[1]中南大学湘雅医院肿瘤科,长沙410008 [2]中山大学附属第六医院肿瘤内科,广州510655

出　　处：《中南大学学报（医学版）》2013年第6期582-589,共8页Journal of Central South University ：Medical Science

基　　金：湖南省自然科学基金(11JJ3115)~~

摘　　要：目的:探讨胃癌组织中3型β微管蛋白(β-tubulin-III,TUBB3)、胸苷酸合成酶(thymidylate synthase,TS)、核苷酸切除修复交叉互补基因(excision repair cross complementation group 1,ERCC1)mRNA表达水平对接受多西他赛/顺铂/氟尿嘧啶(TXT/CDDP/FU,DCF)方案化疗的晚期胃癌患者化疗疗效和预后的影响。方法:共入组48例晚期胃癌患者,所有患者均接受DCF方案姑息化疗。采用分支DNA液相芯片技术对患者胃癌组织中TUBB3,TS,ERCC1 mRNA表达情况进行检测。结果:TUBB3 mRNA低表达患者的化疗缓解率要显著高于高表达患者(P=0.011),而TS和ERCC1表达水平与缓解率无显著性相关。TUBB3 mRNA低表达患者的中位疾病进展时间(TTP)和中位总生存期(OS)均优于高表达患者(P=0.002;P<0.001),TS和ERCC1表达水平与患者的TTP和OS无明显相关。TUBB3,TS,ERCC1中有0或1个基因高表达的患者在化疗缓解率、TTP和OS方面均要优于有2或3个基因高表达的患者(均P=0.001)。Cox回归多因素分析显示:体力状态(Eastern Cooperative Oncology Group,ECOG)评分≥2分(HR=2.42,P=0.009)和TUBB3高表达(HR=2.34,P=0.036)是影响OS的独立不良预后因素。结论:TUBB3 mRNA高表达可能与DCF方案耐药相关,TUBB3可作为接受以TXT为基础化疗的晚期胃癌患者的疗效和预后预测指标。TUBB3,TS和ERCC1 mRNA表达的联合检测有助于晚期胃癌患者的个体化治疗。Objective： To analyze the impact of β-tubulin-Ⅲ （TUBB3）, thymidylate synthase （TS） and excision repair cross complementation group 1 （ERCC1） mRNA expression on chemoresponse and clinical outcome of patients with advanced gastric cancer treated with TXT/CDDP/FU （DCF） regimen chemotherapy. Methods： The study population consisted of 48 patients with advanced gastric cancer. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC 1 of primary tumors were examined by multiplex branched-DNA liquid chip technolog. Results： The patients with low TUBB3 mRNA expression had higher response rate to chemotherapy than patients with high TUBB3 expression （P=0.011）. There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival （OS） and median time to progression （2TP） were significantly longer in patients with low TUBB3 mRNA expression （P=0.002, P〈0.001）. TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TI＇P and OS than the remaining patients （all P〈0.001）. Multivariate analysis revealed that ECOG （Eastern Cooperative Oncology Group）~〉 2 （HR=2.42, P=0.009） and TUBB3 （HR=2.34, P=0.036） mRNA expression significantly impacted on OS. Conclusion： High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 might be a predictive and prognostic factor in patients with advanced gastric cancer treated with TXT-based chemotherapy. The combined evaluation ofTUBB3, TS and ERCC1 expression can promote the individual treatment in advanced gastric cancer.

关 键 词：晚期胃癌 3型β微管蛋白 胸苷酸合成酶 核苷酸切除修复交叉互补基因 药物治疗 

分 类 号：R735.2[医药卫生—肿瘤]