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

检测干细胞样循环肿瘤细胞可提高卵巢癌液体活检的临床适用性

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作者:Snezhanna O Gening, Tatyana V Abakumova, Dina U Gafurbaeva, Albert A Rizvanov, Inna I Antoneeva, Regina R Miftakhova, Andrey B Peskov, Tatyana P Gening

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.

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