Epithelial-mesenchymal transition status of circulating tumor cells in breast cancer and its clinical relevance

Jiaojiao Zhou, Xuan Zhu, Shijie Wu, et al.

Abstract


Objective: Circulating tumor cells (CTCs) play a critical role in cancer metastasis, but their prevalence and significance remainunclear. This study attempted to track the epithelial-mesenchymal transition (EMT) status of CTCs in breast cancer patients andinvestigate their clinical relevance.

Methods: In this study, the established negFACS-IF:E/M platform was applied to isolate rare CTCs and characterize their EMT statusin 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 moreCTCs than stage 0–III patients. Among stage 0–III breast cancers, the HER2 subtype included a significantly higher percentage ofmesenchymal 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. Byapplying a support vector machine (SVM) algorithm, the EMT status of CTCs could distinguish between breast cancer cases withmetastasis/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 specificdetection of CTCs and their EMT traits in breast cancer. This study demonstrated that the EMT status of CTCs had high clinicalrelevance in breast cancer, especially in predicting the distant metastasis or local recurrence of breast cancer.

Cite this article as: Zhou J, Zhu X, Wu S, Guo J, Zhang K, Xu C, et al. Trackingthe epithelial-mesenchymal transition status of circulating tumor cells in breastcancer patients and determining their clinical relevance. Cancer Biol Med.2020; 17: 169-180. doi: 10.20892/j.issn.2095-3941.2019.0118


Keywords


Circulating tumor cells; breast cancer; epithelial-to-mesenchymal transition; estrogen receptor/human epidermal growth factor receptor 2 expression; support vector machine algorithm

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