探讨循环肿瘤细胞的上皮间质转化基因Twist对晚期乳腺癌化疗疗效的影响

目的检测转移性乳腺癌患者外周血循环肿瘤细胞上皮间质转化基因Twist的表达水平及化疗疗效, 探讨Twist对晚期乳腺癌化疗效果的预测意义。方法 应用免疫磁性分选技术(MACS)联合逆转录-聚合酶链反应(RT-PCR)方法检测实验组(58例转移性乳腺癌患者)和对照组(10例健康志愿者)外周血中循环肿瘤细胞(CTCs)Twist基因的表达。分析其与乳腺癌临床病理学参数的关系, 并评估CTCs具有不同Twist基因表达的患者之间治疗效果的差异。结果 在对照组的血液样本中, 未检测出Twist mRNA的表达。在实验组的血液样本中, 19例(32.8%)Twist mRNA表达阳性, 39例(67.2%)Twist mRNA表达阴性。在不同的乳腺癌分子亚型中, 三阴性乳腺癌组的Twist mRNA表达明显高于Luminal A组和Her-2阳性组(P＜0.001)。根据患者化疗后疗效评估结果分析, Twist mRNA表达阳性组患者对化疗的有效率低于阴性组(P＜0.05)。结论 部分循环肿瘤细胞表达Twist基因。发生上皮间质转化的循环肿瘤细胞有更强的抵抗化疗药物的能力, 是三阴性乳腺癌疗效不佳的原因之一。

The significance of epithelial mesenchymal transitions gene Twist in circulating tumor cells to efficacy of chemotherapy in metastatic breast cancer

Objective To detect the level of Twist gene in circulating tumor cells(CTCs)in patients with metastatic breast cancer and evaluate the reaction to treatment of every patient.We tried to discuss the prediction significance of Twist in CTCs to curative effect.Methods We detected the expression of Twist gene in CTCs from 58 metastatic breast cancer(MBC)patients by magnetic activated cell sorting(MACS)technology combined with RT-PCR.We evaluated the clinic significance and the curative effect of chemotherapy in MBC patients using Response Evaluation Criteria in Solid Tumors(RECIST).Results There was no positive expression of Twist mRNA in blood samples from 10 healthy volunteers based on our methods.Among 58 MBC samples, 19/58(32.8%)were found to express Twist mRNA.In three different breast cancer subgroups, Twist mRNA was expressed more frequently in the triple negative subgroups than in luminal A and Her-2 positive subgroups(P＜0.001).After two cycles of chemotherapy, the overall response rate(ORR)of MBC patients to chemotherapy in Twist mRNA positive group was lower than in Twist mRNA negative group(P＜0.05).Conclusion Some CTCs undergo EMT and express epithelial mesenchymal transition gene Twist.CTCs undergoing EMT in breast cancer patients may have a survival advantage because of resistance to chemotherapy.The presence of mesenchymal CTCs predicted resistance to chemotherapy and they maybe one of the reasons of invalid therapy of triple negative breast cancer.