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.
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.
Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xiuwen
X
Guan
Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Fei
F
Ma
SurExam Bio-Tech, Guangzhou Technology Innovation Base, Science City, China.
Suyan
S
Liu
SurExam Bio-Tech, Guangzhou Technology Innovation Base, Science City, China.
Shiyang
S
Wu
SurExam Bio-Tech, Guangzhou Technology Innovation Base, Science City, China.
Rong
R
Xiao
Department of Medical Oncology, Huanxing Cancer Hospital, Beijing, China.
Lifang
L
Yuan
Department of Medical Oncology, Huanxing Cancer Hospital, Beijing, China.
Xiaoying
X
Sun
Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zongbi
Z
Yi
SurExam Bio-Tech, Guangzhou Technology Innovation Base, Science City, China.
Huiyi
H
Yang
Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Binghe
B
Xu
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
breast cancer; circulating tumor cells; epithelial-mesenchymal transition; hormone receptor; subpopulations