Analysis of the hormone receptor status of circulating tumor cell subpopulations based on epithelial-mesenchymal transition: a proof-of-principle study on the heterogeneity of circulating tumor cells
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Xiuwen Guan1, Fei Ma1, Suyan Liu2, Shiyang Wu2, Rong Xiao2, Lifang Yuan3, Xiaoying Sun3, Zongbi Yi1, Huiyi Yang2, Binghe Xu1
1Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2SurExam Bio-Tech, Guangzhou Technology Innovation Base, Science City, China
3Department of Medical Oncology, Huanxing Cancer Hospital, Beijing, China
Fei Ma, email: [email protected]
Keywords: breast cancer, circulating tumor cells, epithelial-mesenchymal transition, hormone receptor, subpopulations
Received: January 27, 2016 Accepted: August 13, 2016 Published: September 01, 2016
Although the enumeration of circulating tumor cells (CTCs) has been demonstrated to be a prognostic indicator in metastatic breast cancer, the heterogeneous characteristics of CTCs, such as variations in the epithelial-mesenchymal transition (EMT), may limit its broad clinical application. To investigate an uncomplicated and practicable detection approach based on the potential utility of the heterogeneity of CTCs from the standpoint of the EMT phenotype and ER/PR status of CTCs, an analysis was conducted using peripheral blood samples obtained from 28 metastatic breast cancer patients. The CanPatrol CTC enrichment technique was used to identify different CTC subpopulations, including epithelial-dominated CTCs, biophenotypic epithelial/mesenchymal CTCs, and mesenchymal-dominated CTCs, according to epithelial and mesenchymal markers. Furthermore, the hormone receptor (HR) status of each CTC was determined based on the expression levels of three reference genes and was characterized by four levels, which ranged from high-level expression to non-expression. We subsequently concluded that based on EMT phenotypes, the order of different CTC subgroups differed according to the HR expression status of the primary tumor. With respect to the HR status between tissues and CTCs, the variation tendency from high-level expression to non-expression of HR in CTCs was significantly correlated with the HR status of the primary tumor. The findings could provide evidence for the potential application of this uncomplicated and practicable detection approach for prognostic analysis and individualized endocrine therapeutic direction in a real-time manner via confirmation in further large-scale trials.
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