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. 2021 Aug 11;11(8):815.
doi: 10.3390/life11080815.

The Detection of Stem-Like Circulating Tumor Cells Could Increase the Clinical Applicability of Liquid Biopsy in Ovarian Cancer

Snezhanna O Gening  1 , Tatyana V Abakumova  1 , Dina U Gafurbaeva  2 , Albert A Rizvanov  2 , Inna I Antoneeva  3 , Regina R Miftakhova  2 , Andrey B Peskov  1 , Tatyana P Gening  1
Affiliations

The Detection of Stem-Like Circulating Tumor Cells Could Increase the Clinical Applicability of Liquid Biopsy in Ovarian Cancer

Snezhanna O Gening et al. Life (Basel). .

Abstract

Stem properties allow circulating tumor cells (CTCs) to survive in the bloodstream and initiate cancer progression. We aimed to assess the numbers of stem-like CTCs in patients with ovarian cancer (OC) before treatment and during first-line chemotherapy (CT). Flow cytometry was performed (Cytoflex S (Beckman Coulter, CA, USA)) using antibodies against CD45; epithelial markers EpCAM and cytokeratin (CK) 8,18; mesenchymal vimentin (vim); and stem-like CD44, CD133 and ALDH. This study included 38 stage I-IV OC patients (median age 66 (Q1-Q3 53-70)). The CK+vim- counts were higher (p = 0.012) and the CD133+ALDHhigh counts were lower (p = 0.010) before treatment in the neoadjuvant CT group than in the adjuvant group. The patients with ascites had more CK+vim- cells before treatment (p = 0.009) and less EpCAM-vim+ cells during treatment (p = 0.018) than the patients without ascites. All the CTC counts did not differ significantly in paired samples. Correlations were found between the CK-vim+ and CD133+ALDHhigh (r = 0.505, p = 0.027) and EpCAM-vim+ and ALDHhigh (r = 0.597, p = 0.004) cells before but not during treatment. Multivariate Cox regression analysis showed that progression-free survival was longer with the presence of surgical treatment (HR 0.06 95% CI 0.01-0.48, p = 0.009) and fewer CD133+ALDHveryhigh cells (HR 1.06 95% CI 1.02-1.12, p = 0.010). Thus, CD133+ALDH+ CTCs have the greatest prognostic potential in OC among the phenotypes studied.

Keywords: ALDH; CD133; CD44; CTCs; EpCAM; circulating tumor cells; cytokeratin; ovarian cancer; stem cells; vimentin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patients’ selection, treatment and sampling within the study.
Figure 2
Figure 2
Identification of different populations of circulating tumor cells: (a) discrimination by CD45 binding intensity; (b) assessment of the ALDH expression intensity within the CD45-CD133+ population.
Figure 3
Figure 3
Statistically significant (*) differences in CTC counts between groups: (a,b) differences between groups of neoadjuvant vs. adjuvant therapy; (c,d) differences between groups with and without ascites. Data are presented as median and interquartile range.
Figure 4
Figure 4
Correlation matrix for the CTC counts before and during treatment.
See this image and copyright information in PMC

References

    1. Arnold M., Rutherford M.J., Bardot A., Ferlay J., Andersson T.M.-L., Myklebust T.Å., Tervonen H., Thursfield V., Ransom D., Shack L., et al. Progress in Cancer Survival, Mortality, and Incidence in Seven High-Income Countries 1995–2014 (ICBP SURVMARK-2): A Population-Based Study. Lancet Oncol. 2019;20:1493–1505. doi: 10.1016/S1470-2045(19)30456-5. - DOI - PMC - PubMed
    1. Schwarz R.F., Ng C.K.Y., Cooke S.L., Newman S., Temple J., Piskorz A.M., Gale D., Sayal K., Murtaza M., Baldwin P.J., et al. Spatial and Temporal Heterogeneity in High-Grade Serous Ovarian Cancer: A Phylogenetic Analysis. PLoS Med. 2015;12:e1001789. doi: 10.1371/journal.pmed.1001789. - DOI - PMC - PubMed
    1. Lee C.K., Asher R., Friedlander M., Gebski V., Gonzalez-Martin A., Lortholary A., Lesoin A., Kurzeder C., Largillier R., Hilpert F., et al. Development and Validation of a Prognostic Nomogram for Overall Survival in Patients with Platinum-Resistant Ovarian Cancer Treated with Chemotherapy. Eur. J. Cancer. 2019;117:99–106. doi: 10.1016/j.ejca.2019.05.029. - DOI - PubMed
    1. van de Laar R., IntHout J., Van Gorp T., Verdonschot S., van Altena A.M., Gerestein C.G., Massuger L.F.A.G., Zusterzeel P.L.M., Kruitwagen R.F.P.M. External Validation of Three Prognostic Models for Overall Survival in Patients with Advanced-Stage Epithelial Ovarian Cancer. Br. J. Cancer. 2014;110:42–48. doi: 10.1038/bjc.2013.717. - DOI - PMC - PubMed
    1. Cortés-Hernández L.E., Eslami-S Z., Alix-Panabières C. Circulating Tumor Cell as the Functional Aspect of Liquid Biopsy to Understand the Metastatic Cascade in Solid Cancer. Mol. Asp. Med. 2020;72:100816. doi: 10.1016/j.mam.2019.07.008. - DOI - PubMed