:Background: Current diagnosis and staging of advanced epithelial ovarian cancer (aEOC) has important limitations and better biomarkers are needed. We investigate the performance of non-haematopoietic circulating cells (CCs) at the time of disease presentation and relapse. Methods: Venous blood was collected prospectively from 37 aEOC patients and 39 volunteers. CCs were evaluated using ImageStream TechnologyTM and specific antibodies to differentiate epithelial cells from haematopoetic cells. qRT-PCR from whole blood of relapsed aEOC patients was carried out for biomarker discovery. Results: Significant numbers of CCs (CK+/WT1+/CD45-) were identified, quantified and characterised from aEOC patients compared to volunteers. CCs are abundant in women with newly diagnosed aEOC, prior to any treatment. Evaluation of RNA from the CCs in relapsed aEOC patients (n = 5) against a 79-gene panel revealed several differentially expressed genes compared to volunteers (n = 14). Size differentiation of CCs versus CD45+ haematopoietic cells was not reliable. Conclusion: CCs of non-haematopoetic origin are prevalent, particularly in patients with newly diagnosed aEOC. Exploiting a CC-rich population in aEOC patients offers insights into a part of the circulating microenvironment.

Department Life Sciences Brunel University London Uxbridge UB8 3PH UK

Department of Oncology and Reconstructive Surgery Sechenov 1st Moscow State Medical University 119146 Moscow Russia

Division of Thoracic Surgery The Royal Brompton and Harefield NHS Foundation Trust Harefield Hospital London UB9 6JH UK

Faculty of Health and Medical Sciences School of Biosciences and Medicine University of Surrey Guildford Surrey GU2 7XH UK

Laboratory of Gene Expression Institute of Biotechnology CAS v v i 252 50 Vestec Czech Republic

Mount Vernon Cancer Centre Middlesex HA6 2RN UK

TATAA Biocenter 411 03 Göteborg Sweden

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