Spectrum of epithelial-mesenchymal transition phenotypes in circulating tumour cells from early breast cancer patients

Aleksandra Markiewicz , Justyna Topa , Anna Nagel , Jarosław Skokowski , Barbara Seroczynska , Tomasz Stokowy , Marzena Wełnicka-Jaśkiewicz , Anna Żaczek

Abstract

Circulating tumour cells (CTCs) can provide valuable prognostic information in a number of epithelial cancers. However, their detection is hampered due to their molecular heterogeneity, which can be induced by the epithelial-mesenchymal transition (EMT) process. Therefore, current knowledge about CTCs from clinical samples is often limited due to an inability to isolate wide spectrum of CTCs phenotypes. In the current work, we aimed at isolation and molecular characterization of CTCs with different EMT status in order to establish their clinical significance in early breast cancer patients. We have obtained CTCs-enriched blood fraction from 83 breast cancer patients in which we have tested the expression of epithelial, mesenchymal and general breast cancer CTCs markers (MGB1/HER2/CK19/CDH1/CDH2/VIM/PLS3), cancer stem cell markers (CD44, NANOG, ALDH1, OCT-4, CD133) and cluster formation gene (plakoglobin). We have shown that in the CTCs-positive patients, epithelial, epithelial-mesenchymal and mesenchymal CTCs markers were detected at a similar rate (in 28%, 24% and 24%, respectively). Mesenchymal CTCs were characterized by the most aggressive phenotype (significantly higher expression of CXCR4, uPAR, CD44, NANOG, p < 0.05 for all), presence of lymph node metastases (p = 0.043), larger tumour size (p = 0.023) and 7.33 higher risk of death in the multivariate analysis (95% CI 1.06–50.41, p = 0.04). Epithelial-mesenchymal subtype, believed to correspond to highly plastic and aggressive state, did not show significant impact on survival. Gene expression profile of samples with epithelial-mesenchymal CTCs group resembled pure epithelial or pure mesenchymal phenotypes, possibly underlining degree of EMT activation in particular patient’s sample. Molecular profiling of CTCs EMT phenotype provides more detailed and clinically informative results, proving the role of EMT in malignant cancer progression in early breast cancer.
Author Aleksandra Markiewicz (IFB)
Aleksandra Markiewicz,,
- Intercollegiate Faculty of Biotechnology UG
, Justyna Topa (IFB)
Justyna Topa,,
- Intercollegiate Faculty of Biotechnology UG
, Anna Nagel (IFB)
Anna Nagel,,
- Intercollegiate Faculty of Biotechnology UG
, Jarosław Skokowski
Jarosław Skokowski,,
-
, Barbara Seroczynska
Barbara Seroczynska,,
-
, Tomasz Stokowy
Tomasz Stokowy,,
-
, Marzena Wełnicka-Jaśkiewicz
Marzena Wełnicka-Jaśkiewicz,,
-
, Anna Żaczek (IFB / DMedB)
Anna Żaczek,,
- Department of Medical Biotechnology
Journal seriesCancers, ISSN 2072-6694, (0 pkt)
Issue year2019
Vol11
No1
Pages1-19
Publication size in sheets0.9
Article number59
Keywords in Englishcirculating tumour cells, epithelial-mesenchymal transition, cancer stem cell markers, breast cancer, prognostic factor
ASJC Classification1306 Cancer Research; 2730 Oncology
DOIDOI:10.3390/cancers11010059
URL https://doi.org/10.3390/cancers11010059
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)5
ScoreMinisterial score = 0.0, 31-05-2019, ArticleFromJournal
Ministerial score (2013-2016) = 5.0, 31-05-2019, ArticleFromJournal - czasopismo zagraniczne spoza list
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.403; WoS Impact Factor: 2017 = 5.326 (2)
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