Luminal B型局部晚期乳腺癌新辅助化疗疗效预测基因的研究  

Identify genetic predictive factors for neoadjuvant chemotherapy in patients with luminal B type locally advanced breast cancer

作　　者：王梅[1] 汪海新 胡薇[3] 熊安稳[1] 吴梅红[1] 李永梅[1] 王薇[1] 王雅杰[1] 

机构地区：[1]第二军医大学附属长海医院肿瘤科,上海200433 [2]解放军第371医院肿瘤科,453000 [3]第二军医大学附属长海医院乳腺外科,上海200433

出　　处：《临床肿瘤学杂志》2014年第5期401-406,共6页Chinese Clinical Oncology

基　　金：上海市自然科学基金资助项目(10ZR3814100)

摘　　要：目的筛选Luminal B型局部晚期乳腺癌新辅助化疗疗效预测基因。方法收集10例Luminal B型乳腺癌患者,均行DA方案新辅助化疗(多西他赛75mg/m2静滴,d1;表阿霉素80mg/m2静滴d1,21天为1周期,共4个周期),根据化疗疗效分为完全病理缓解(pCR)组(n=3)和非完全病理缓解(npCR)组(n=7)。采用人基因表达谱cDNA芯片从10例乳腺癌患者中筛选新辅助化疗疗效相关基因,荧光定量PCR验证差异表达基因。结果 pCR组与npCR组癌组织相比,上调基因231个,下调基因195个;pCR组癌组织与癌旁组织相比,上调的基因357个,下调的基因544个;npCR组癌组织与癌旁组织相比,上调基因143个,下调基因101个;pCR组与npCR组癌旁组织比较,上调基因98个,下调基因67个。pCR组与npCR组癌组织比较,筛选出6个与肿瘤有关的基因,其中上调基因为CYP4Z1、FGFL6、BCAR4,下调基因为FABP4、S100B、ALPH1L1。荧光定量PCR进一步验证显示,两组mRNA表达差异的基因为CYP4Z1和BCAR4,pCR组两种基因表达均显著低于npCR组(P<0.05)。结论对局部晚期Luminal B型乳腺癌低表达BCAR4和CYP4Z1的患者新辅助治疗选择采用DA方案化疗更有可能获得pCR。Objective To screen prognostic genes for neoadjuvant chemotherapy in patients with locally advanced breast cancer of luminal B type. Methods Ten locally advanced breast cancer patients of luminal B type were underwent DA regimen as neoadjuvant chemotherapy（ docetaxel 75mg/m2 iv, d1;epirubicin 80 mg/m2 iv, d1 , 3 weeks as a cycle for 4 cycles） . Based on RECIST1.1 standard, 10 patients were divided into pathological complete remission（ pCR） group（ n=3） and non-pathological complete remission（ npCR） group （ n=7） . GeneChip human genome was used to screen prognostic genes for neoadjuvant chemotherapy in 10 luminal B breast cancer pa-tients. Florescence quantitative PCR was conducted to confirm the different gene expression. Results Compared with npCR patients, 231 genes expression were upregulated, 195 genes expression were down-regulated in tumor samples of pCR patients;Compared with peri-tumor tissues, 357 genes expression were up-regulated and 544 genes expression were down-regulated in tumor samples of pCR patients. Compared with peri-tumor tissues, 143 genes expression were up-regulated and 101 genes expression were down-regulated in the tumor samples of npCR patients. Compared with npCR patients, 98 genes expression were up-regulated and 67 genes expression were down-regu-lated in peri-tumor samples of pCR patients. Statistically significant differences in gene expressions were noted in pCR group vs. npCR group, including 3 up-regulated genes of CYP4Z1, FGFL6 and BCAR4, as well as 3 down-regulated genes of FABP4, S100B and AL-PH1L1. The expression of CYP4Z1 and BCAR4 in pCR patients was significantly lower than that of npCR patients（P〈0.05） confirmed by florescence quantitative PCR. Conclusion In patients with luminal B locally advanced breast cancer, lower expression of CYP4Z1 and BCAR4 may be associated with higher pCR rates in neoadjuvant chemotherapy receiving DA regimen.

关 键 词：LUMINAL B 型 局部晚期乳腺癌 新辅助化疗 基因芯片检测 

分 类 号：R737.9[医药卫生—肿瘤]