Circulating tumour cells are a prognostic indicator in advanced high-grade serous ovarian cancer and are associated with platelets and immune cells following dissemination

Sep 29, 2026

Circulating tumour cells (CTCs) are rare yet crucial biomarkers with significant prognostic potential across cancers, but their role in high-grade serous ovarian cancer (HGSC) remains unclear. To define the spectrum of CTCs in HGSC, EpCAM-independent enrichment was applied to advanced patients, assessing prognostic value and molecular signatures. CTC enumeration used Parsortix and ovarian vein sampling, followed by FACS single-cell sorting and scRNAseq. Peripheral CTC detection predicted worse progression-free survival, CTC clusters associated with platelets/immune cells, and immune-related gene enrichment was observed.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Background

Methods

Results

Conclusions

Introduction

[www.nature.com/bjc](www.nature.com/bjc British)[ British](www.nature.com/bjc British) Journal of Cancer ARTICLE OPEN Cellular and Molecular Biology Circulating tumour cells are a prognostic indicator in advanced high-grade serous ovarian cancer and are associated with platelets and immune cells following dissemination Mark P. Ward 1,2,3 ✉, Faye Lewis1,2,3, Catherine O’Gorman3,4, Lucy A. Norris3,4, Sarah E. Lochrin3,5, Laura E. Kane 1,2,3, Tanya E. Kelly1,2,3, Bashir M. Mohamed1,2,3, Ashitha Ramesh1,2,3, Roisin O’Connor1,2,3, Elaine Kilgour6, Brian Henderson 1,2,3, Marika Kanjuga1,2,3, Sinead Hurley1,2,3, Laura Edgerton1,2,3, Prerna Tewari1,2,3, Kathy Gately3,7, Lorraine O’Driscoll 3,8, Karsten Hokamp9, Siobhan Cashman 10, Gavin McManus 11, Doug A. Brooks 2,12, Stavros Selemidis13, Niamh Coleman3,5, John John Kennedy3,5, Waseem Kamran3,14, James P. Beirne3,14, Patrick Maguire3,14, Feras Abu Saadeh3,14, Karen Cadoo3,5, Cara M. Martin1,2,3, J. O’Leary1,2,3,15 ✉ and Sharon A. O’Toole1,2,3,4,15 ✉ © The Author(s) 2025 | | 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: CTCs isolated using Parsortix® enrichment in HGSC ranged between 1-22 cells/7.5 ml blood. Concordance was seen between Parsortix® enrichment and CellSearch® enumeration in patients with MBC (R2 = 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. | | | | | British Journal of Cancer (2026) 134:22–32; [https://doi.org/10.1038/s41416-025-03227-7](https://doi.org/10.1038/s41416-025-03227-7) | | | | | | INTRODUCTION Circulating tumour cells (CTCs) are rare haematogenous circulating epithelial derived cancer cells that are released into the blood circulation and represent a critical intermediate phase of the metastatic cascade [1] . CTCs are a prognostic indicator in metastatic breast, colorectal and prostate cancers, with higher numbers of CTCs predicting shorter disease-free intervals and overall survival [2–4] . However, CTCs are rare and vary 1Molecular Pathology Research Lab, Coombe Women and Infants University Hospital, Dublin 8, Ireland. 2Department

FAQs

What is the study focus regarding circulating tumour cells (CTCs) in HGSC?

The study examines whether CTCs in advanced high-grade serous ovarian cancer can serve as prognostic indicators and investigates their molecular signatures and associations with platelets and immune cells.

How were CTCs enriched and analyzed in patients with HGSC?

CTC enumeration was performed using Parsortix CTC enrichment in newly diagnosed HGSC patients, and CTCs were also isolated from the ovarian vein. FACS single-cell sorting and scRNAseq were performed on ovarian vein CTCs.

What key findings link CTCs to prognosis and immune involvement?

CTC detection in HGSC predicted poorer progression-free survival. CTC clusters were isolated from the ovarian vein, cloaked in platelets and immune cells, and scRNAseq showed enrichment in genes associated with immune signalling.

Sep 29, 2026

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