Mark P. Ward, Faye Lewis, Catherine O’Gorman, Lucy Norris, Sarah E. Lochrin, Laura Kane, Tanya Kelly, Bashir M. Mohamed, Ashitha Ramesh, Roisin O’Connor, Elaine Kilgour, Brian E. Henderson, Marika Kanjuga, Sinéad Hurley, Laura Bogue Edgerton, Prerna Tewari, Kathy Gately, Lorraine O’Driscoll, Karsten Hokamp, Siobhan M. Cashman, Gavin McManus, Doug A. Brooks, Stavros Selemidis, Niamh Coleman, John Kennedy, Waseem Kamran, James Beirne, Patrick Maguire, Feras Abu Saadeh, Karen A. Cadoo, Cara Martin, John O’Leary, Sharon O’Toole
BACKGROUND: Circulating tumour cells (CTCs) are rare yet crucial biomarkers with significant prognostic potential across different cancer types. However, their role in high-grade serous ovarian cancer (HSGC) is not well defined. To capture the full spectrum of CTCs found in HGSC, we employed an EpCAM independent enrichment technique in patients with advanced HGSC and investigated the prognostic value and molecular signatures of these rare cells. METHODS: CTC enumeration was performed in 43 newly diagnosed patients with HGSC using Parsortix® CTC enrichment and benchmarked against a metastatic breast cancer (MBC) cohort for which the device is FDA approved. CTCs were also isolated from the ovarian vein of patients with HGSC during primary cytoreductive surgery. CTCs were assessed as prognostic markers in patients with HGSC. FACS single cell sorting and scRNAseq was performed on CTCs isolated from the ovarian vein. RESULTS: = 0.8786). CTC clusters were isolated from the ovarian vein (P = 0.0195) and were cloaked in platelets/immune cells. Detection of CTCs in patients with HGSC was predictive of a poorer progression free survival (P = 0.0183). Patients with CTCs were found to have increased serum levels of CD73 (P = 0.0311). scRNAseq of CTCs isolated from the ovarian vein identified enrichment in genes associated with immune signalling. CONCLUSIONS: Peripheral CTCs isolated from patients with HGSC were predictors of a poor prognosis. The ovarian vein was found to be a rich source of disseminating CTC clusters in HGSC. Further studies are warranted to investigate the utility of CTCs as markers of neoadjuvant chemotherapy response as well as for longitudinal monitoring. Molecular analysis of CTCs in HGSCs reveals a potential role of the immune system in CTC-mediated haematogenous metastasis.