BRCA1、ERCC1、TYMS及TUBB3基因检测指导进展期胃癌个体化化疗效果观察

摘要

目的 观察用胃癌组织BRCA1、ERCC1、TYMS、TUBB3的表达情况指导进展期胃癌个体化化疗的效果.方法 前瞻性纳入进展期胃癌患者80例,随机分为个体组和对照组,各40例.个体组均用免疫组化法检测胃癌组织BRCA1、ERCC1、TYMS、TUBB3蛋白,用分支DNA液相芯片技术检测胃癌组织BRCA1、ERCC1、TYMS、TUBB3 mRNA表达,并根据检测结果 选择个体化化疗方案(BRCA1、ERCC1阳性不用铂类药物,TYMS阳性不用氟尿嘧啶类药物,TUBB3阳性不用紫杉类药物).对照组一律采用DCF或改良DCF方案化疗.比较两组治疗效果及不良反应.结果2周期化疗后个体组、对照组化疗总体有效率(ORR)分别为41.9%、39.4%,KPS获益率分别为54.8%、54.5%,两组相比P均>0.05.4周期化疗后个体组、对照组ORR分别为45.0%和54.5%,KPS获益率分别为75.0%和72.7%,两组相比P均>0.05.两组均无化疗相关性死亡.两组各类型3~4级不良反应发生率相比P均>0.05.个体组9例(26.3%)、对照组19例(55.9%)因不良反应减量或停止化疗,两组因不良反应减量或停止化疗发生率相比,P<0.05.个体组、对照组无进展生存期(PFS)分别为7.7(95%CI为5.97~9.42)、6.6(95%CI为5.59~7.6)个月,两组PFS相比P>0.05.结论 与单纯应用DCF或改良DCF方案相比,用胃癌组织BRCA1、ERCC1、TYMS、TUBB3的表达情况指导进展期胃癌个体化化疗的不良反应较少,但二者疗效和预后比较无统计学差异.%Objective To investigate the effects of detection of BRCA 1, ERCC1, TYMS and TUBB3 genes in guid-ance of individual chemotherapy for patients with advanced gastric cancer .Methods Eighty patients with advanced gastric cancer were randomly divided into the individual group (TG) (n=40) and the control group (CG) (n=40).The protein and mRNA expression levels of BRCA1, ERCC1, TYMS and TUBB3 genes were measured by immunohistochemical method and branched-DNA liquid chip quantitative analysis , respectively .Different chemotherapies were administered according to the mRNA expression levels of the four genes , while DCF or mDCF chemotherapy was directly applied to the control group . Overall response rate ( ORR) , adverse effects , and progression-free survival ( PFS) were observed and analyzed .Results After two cycles, ORR were 41.9%in the TG and 39.4%in the CG.KPS clinical benefit rates were 54.8%in the TG and 54.5%in the CG.There were no statistical differences between two groups (both P>0.05).After four cycles, ORR were 45%in the TG and 54.5%in the CG, and KPS clinical benefit rates were 75.0%in the TG and 72.7%in the CG. There were no statistical differences between two groups (both P>0.05).The rates of adverse effects in grade 3 to 4 were 26.3%and 55.9% in the TG and CG, respectively.There was no statistical difference between the two groups ( P>0.05), but adverse effects were significantly less serious in TG than in CG after dose reduction and chemotherapy discon -tinuance (P<0.05).PFS were 7.7 m (95%CI:5.97-9.42) and 6.6 m (95%CI:5.59-7.6) in the TG and CG.There was no statistically significant difference between the two groups (P>0.05).Conclusion Compared with DCF or mDCF chemotherapy, using their BRCA1, ERCC1, TYMS and TUBB3 mRNA expression levels in guidance of the individual chemotherapy for patients with advanced gastric cancer may reduce the adverse effects , but there are no statistical differ-ences in the ORR and PFS .