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Neutrophil activation markers as novel biomarkers for advanced stages of high-grade serous ovarian cancer

1Medical Research Institute Hospital La Fe, Valencia, Comunidad Valenciana, Spain, 2Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, Valencia, Comunidad Valenciana, Spain, 3Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Comunidad Valenciana, Spain, 4Obstetrics and Gynaecology Service, General University Hospital of Valencia Consortium, Valencia, Comunidad Valenciana, Spain, 5Obstetrics and Gynaecology Service, General University Hospital of Castellón, Castellón, Comunidad Valenciana, Spain, 6Pathological Anatomy Service, General University Hospital of Valencia Consortium, Valencia, Comunidad Valenciana, Spain, 7Medical Oncology Service, General University Hospital of Valencia Consortium, Valencia, Comunidad Valenciana, Spain, 8Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery (MUAPOS), General University Hospital of Castellón, Valencia, Comunidad Valenciana, Spain, 9Departament of Paediatrics, Obstetrics and Gynaecology, University of Valencia, Valencia, Comunidad Valenciana, Spain

Abstract Number: PB0731

Meeting: ISTH 2022 Congress

Theme: Hemostatic Systems in Cancer, Inflammation and Immunity » Coagulation Proteins Beyond Hemostasis

Background: In the tumor environment, NETosis participates in immunothrombosis, tumor progression, metastasis, and immune evasion. NETosis has been only evidenced in the initial metastasis of high-grade serous ovarian cancer (HGSOC).

Aims: To ascertain the contribution of NETosis in advanced stages of HGSOC and as a diagnostic biomarker.

Methods: In paired plasma and peritoneal fluid (PF) samples from women with advanced HGSOC (n=28) and controls (n=16), we quantified as NETosis markers: circulating DNA (cfDNA, Quant-iT PicoGreen dsDNA kit), nucleosomes (Cell Death Detection ELISAPLUS kit), calprotectin (Human Calprotectin ELISA kit) and myeloperoxidase (MPO, Human MPO ELISA kit). We estimated their differences with SPSS software (v.21).

Results: Patients with HGSOC presented a higher concentration of cfDNA in plasma than controls (p < 0.001) and an increase in all 4 NETosis markers in PF (Fig.1). All markers correlated pairwise in both biofluids (p < 0.032) and with plasma neutrophil count (p < 0.001). Remarkably, plasma cfDNA could distinguish patients from controls (AUC=0.842). Interestingly, among HGSOG patients, those who previously received neoadjuvant treatment (n=7) presented decreased levels of NETosis markers, predominantly in plasma and not in PF (Fig.2).

Conclusion(s): For the first time, we describe an increase in NETosis markers in PF of advanced HGSOC, which could reflect the contribution of NETosis in its development in the pelvic microenvironment. Plasma cfDNA could represent a minimally invasive diagnostic biomarker for HGSOC that could reduce the pre-surgical rate of false positives. Our observation that NETosis biomarkers mainly decrease in plasma as consequence of neoadjuvant treatment might involve that, at least for NETosis process, the intravenous administration of chemotherapy would produce more changes at the systemic level (plasma) than in the peritoneal tumor environment (PF). This could deserve a reflection on the role of intraperitoneal chemotherapy in the management of HGSOC patients. ISCIII-FEDER (PI17/01945, PI20/00075), GV/2020/200, Premio FIHGUV 2019 and 2020, APOSTD/2019/087, ACIF/2020/216, SETH.

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Figure 1.

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Figure 2.

To cite this abstract in AMA style:

Oto J, Mc Cormack B, Tomás-Pérez S, Fernández-Pardo A, González-Cantó E, Cana F, Aghababyan C, Herranz R, Cañete-Mota S, Cuadros-Lozano A, Martínez-Fernández L, Aranda-Borreda A, Arroyo-Álvarez A, Santonja-López N, Ramírez-Belloch R, Llueca-Abella A, Marí-Alexandre J J, Gilabert-Estellés J, Medina P. Neutrophil activation markers as novel biomarkers for advanced stages of high-grade serous ovarian cancer [abstract]. https://abstracts.isth.org/abstract/neutrophil-activation-markers-as-novel-biomarkers-for-advanced-stages-of-high-grade-serous-ovarian-cancer/. Accessed September 21, 2023.

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