临床肿瘤学杂志

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Luminal B型局部晚期乳腺癌新辅助化疗疗效预测基因的研究

王 梅1,汪海新2,胡 薇3,熊安稳1,吴梅红1,李永梅1,王 薇1,王雅杰1   

  1. 1 200433 上海 第二军医大学附属长海医院肿瘤科2 453000 解放军第371医院肿瘤科3 200433 第二军医大学附属长海医院乳腺外科
  • 收稿日期:2013-12-05 修回日期:2014-03-09 出版日期:2014-05-31 发布日期:2014-05-31
  • 通讯作者: 王雅杰

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

WANG Mei, WANG Haixin, HU Wei, XIONG Anwen, WU Meihong, LI Yongmei, WANG Wei, WANG Yajie.   

  1. Department of Oncology,Changhai Hospital, the Second Military Medical University, Shanghai 200433, China
  • Received:2013-12-05 Revised:2014-03-09 Online:2014-05-31 Published:2014-05-31
  • Contact: WANG Yajie

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。

Abstract: 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/m2iv, 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 patients. Florescence quantitative PCR was conducted to confirm the different gene expression. Results Compared with npCR patients, 231 genes expression were up-regulated, 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regulated 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 ALPH1L1. 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.

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