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British journal of cancer · 2025

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

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Ward Mark P, Lewis Faye, O'Gorman Catherine, Norris Lucy A, Lochrin Sarah E, Kane Laura E, Kelly Tanya E, Mohamed Bashir M, Ramesh Ashitha, O'Connor Roisin, Kilgour Elaine, Henderson Brian, Kanjuga Marika, Hurley Sinead, Edgerton Laura, Tewari Prerna, Gately Kathy, O'Driscoll Lorraine, Hokamp Karsten, Cashman Siobhan, McManus Gavin, Brooks Doug A, Selemidis Stavros, Coleman Niamh, Kennedy John, Kamran Waseem, Beirne James P, Maguire Patrick, Abu Saadeh Feras, Cadoo Karen, Martin Cara M, O'Leary John J, O'Toole Sharon A

Аннотация

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.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты