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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

Ovarian Cancer (OC) is one of the leading causes of death among gynecological tumors and there is still an insufficient understanding of its evolution. Blood, as a minimal invasive tool, allows multiple sampling over the treatment course and genomic single circulating tumor cell (sCTC) data provide the opportunity to investigate the genetic tumor evolution. CTC detection in OC remains difficult, due to epithelial-mesenchymal transition (EMT). This proof of principle study presents a workflow to generate sCTC genomic data, with the need of further studies to improve the CTC detection rate and enable insights into tumor evolution on a sCTC resolution to identify new treatment targets and/or biomarkers for an early treatment intervention.

Abstract

In Ovarian Cancer (OC), the analysis of single circulating tumor cells (sCTCs) might help to investigate genetic tumor evolution during the course of treatment. Since common CTC identification features failed to reliably detect CTCs in OC, we here present a workflow for their detection and genomic analysis. Blood of 13 high-grade serous primary OC patients was analyzed, using negative immunomagnetic enrichment, followed by immunofluorescence staining and imaging for Hoechst, ERCC1, CD45, CD11b and cytokeratin (CK) and sCTC sorting with the DEPArrayTM NxT. The whole genome of single cells was amplified and profiled for copy number variation (CNV). We detected: Type A-cells, epithelial (Hoechstpos, ERCC1pos, CD45neg, CD11bpos, CKpos); Type B-cells, potentially epithelial (Hoechstpos, ERCC1pos, CD45neg, CD11bpos, CKneg) and Type C-cells, potentially mesenchymal (Hoechstpos, ERCC1pos, CD45neg, CD11bneg, CKneg). In total, we identified five (38.5%) patients harboring sCTCs with an altered CN profile, which were mainly Type A-cells (80%). In addition to inter-and intra-patient genomic heterogeneity, high numbers of Type B- and C-cells were identified in every patient with their aberrant character only confirmed in 6.25% and 4.76% of cases. Further identification markers and studies in the course of treatment are under way to expand sCTC analysis for the identification of tumor evolution in OC.

Details

Title
Image-Based Identification and Genomic Analysis of Single Circulating Tumor Cells in High Grade Serous Ovarian Cancer Patients
Author
Salmon, Carolin 1   VIAFID ORCID Logo  ; Levermann, Janina 1 ; Neves, Rui P L 2   VIAFID ORCID Logo  ; Sven-Thorsten Liffers 3 ; Kuhlmann, Jan Dominik 4 ; Buderath, Paul 1 ; Kimmig, Rainer 1 ; Kasimir-Bauer, Sabine 1   VIAFID ORCID Logo 

 Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany; [email protected] (J.L.); [email protected] (P.B.); [email protected] (R.K.); [email protected] (S.K.-B.) 
 Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany; [email protected] 
 West German Cancer Center, Bridge Institute of Experimental Tumor Therapy, University Medicine Essen, 45147 Essen, Germany; [email protected]; German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Partner Site Essen, Division of Solid Tumor Translational Oncology, 69120 Heidelberg, Germany 
 Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; [email protected]; German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; National Center for Tumor Diseases (NCT), 01307 Dresden, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; Helmholtz-Zentrum Dresden—Rossendorf (HZDR), 01307 Dresden, Germany 
First page
3748
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2558718092
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.