Epithelial-mesenchymal transition status of circulating tumor cells in breast cancer and its clinical relevance
Epithelial-mesenchymal transition status of circulating tumor cells in breast cancer and its clinical relevance
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乳腺癌循环肿瘤细胞上皮-间质转化状态及其临床意义
DOI：
10.20892/j.issn.2095-3941.2019.0118
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发表时间：
2020-02-01
影响因子：
5.5
通讯作者：
Chen, Yiding
中科院分区：
文献类型：
--
作者：
Zhou, Jiaojiao;Zhu, Xuan;Chen, Yiding
目的：循环肿瘤细胞（CTC）在肿瘤转移中起着关键作用，但其发生率和意义尚不清楚。本研究试图追踪乳腺癌患者中CTC的上皮-间质转化（EMT）状态，并研究其临床相关性。方法：本研究应用已建立的EMTFACS-IF：E/M平台分离乳腺癌中罕见的CTCs并表征其EMT状态。共招募了89名乳腺癌患者，包括0-III期（n = 60）和晚期（n = 29）病例。结果如下：使用FACS-IF：E/M平台，发现在人表皮生长因子受体2（HER 2）+患者中，间充质CTC通常表现出高百分比的HER 2+细胞。IV期乳腺癌患者具有比0-III期患者多得多的CTC。在0-III期乳腺癌中，HER 2亚型包括比管腔A或B亚型显著更高百分比的间充质和双表型（上皮和间充质）CTC。在IV期患者中，局部复发病例中CTC主要为上皮细胞，远处转移病例中CTC更多为间质细胞。通过应用支持向量机（SVM）算法，CTC的EMT状态可以区分有转移/局部复发的乳腺癌病例和无复发的乳腺癌病例。结论：ERFACS-IF：E/M平台为乳腺癌中CTC及其EMT性状的高灵敏度和特异性检测提供了灵活且普遍可接受的方法。本研究表明，CTCs的EMT状态在乳腺癌中具有高度的临床相关性，特别是在预测乳腺癌的远处转移或局部复发方面。
Objective: Circulating tumor cells (CTCs) play a critical role in cancer metastasis, but their prevalence and significance remain unclear. This study attempted to track the epithelial-mesenchymal transition (EMT) status of CTCs in breast cancer patients and investigate their clinical relevance. Methods: In this study, the established negFACS-IF:E/M platform was applied to isolate rare CTCs and characterize their EMT status in breast cancer. A total of 89 breast cancer patients were recruited, including stage 0–III (n = 60) and late stage (n = 29) cases. Results: Using the negFACS-IF:E/M platform, it was found that in human epidermal growth factor receptor 2 (HER2)+ patients, mesenchymal CTCs usually exhibited a high percentage of HER2+ cells. Stage IV breast cancer patients had considerably more CTCs than stage 0–III patients. Among stage 0–III breast cancers, the HER2 subtype included a significantly higher percentage of mesenchymal and biphenotypic (epithelial and mesenchymal) CTCs than the luminal A or B subtypes. Among stage IV patients, CTCs were predominantly epithelial in cases with local recurrence and were more mesenchymal in cases with distant metastasis. By applying a support vector machine (SVM) algorithm, the EMT status of CTCs could distinguish between breast cancer cases with metastasis/local recurrence and those without recurrence. Conclusions: The negFACS-IF:E/M platform provides a flexible and generally acceptable method for the highly sensitive and specific detection of CTCs and their EMT traits in breast cancer. This study demonstrated that the EMT status of CTCs had high clinical relevance in breast cancer, especially in predicting the distant metastasis or local recurrence of breast cancer.