Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients' biofluids: Potential role in disease diagnosis and management.

NETosis biomarkers calprotectin cfDNA high-grade serous ovarian cancer peritoneal fluid

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 29 11 2022
accepted: 27 01 2023
entrez: 23 2 2023
pubmed: 24 2 2023
medline: 3 3 2023
Statut: epublish

Résumé

High-grade serous ovarian cancer (HGSOC) is the second most frequent gynecological malignancy but the most lethal, partially due to the spread of the disease through the peritoneal cavity. Recent evidence has shown that, apart from their role in immune defense through phagocytosis and degranulation, neutrophils are able to participate in cancer progression through the release of neutrophil extracellular traps (NETs) in a process called NETosis. NETs are composed of DNA, histones, calprotectin, myeloperoxidase (MPO) and elastase and the NETosis process has been proposed as a pre-requisite for the establishment of omental metastases in early stages of HGSOC. Nevertheless, its role in advanced stages remains to be elucidated. Therefore, our principal aim is to characterize a NETosis biomarker profile in biofluids from patients with advanced HGSOC and control women. Specifically, five biomarkers of NETosis (cell-free DNA (cfDNA), nucleosomes, citrullinated histone 3 (citH3), calprotectin and MPO) were quantified in plasma and peritoneal fluid (PF) samples from patients (n=45) and control women (n=40). Our results showed that HGSOC patients presented a higher concentration of cfDNA, citH3 and calprotectin in plasma and of all five NETosis biomarkers in PF than control women. Moreover, these biomarkers showed a strong ability to differentiate the two clinical groups. Interestingly, neoadjuvant treatment (NT) seemed to reduce NETosis biomarkers mainly systemically (plasma) compared to the tumor environment (PF). In conclusion, NETosis biomarkers are present in the tumor environment of patients with advanced HGSOC, which might contribute to the progression of the disease. Besides, plasma cfDNA and calprotectin could represent minimally invasive surrogate biomarkers for HGSOC. Finally, NT modifies NETosis biomarkers levels mainly at the systemic level.

Identifiants

pubmed: 36817483
doi: 10.3389/fimmu.2023.1111344
pmc: PMC9936152
doi:

Substances chimiques

Histones 0
Biomarkers 0
Cell-Free Nucleic Acids 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1111344

Informations de copyright

Copyright © 2023 Tomás-Pérez, Oto, Aghababyan, Herranz, Cuadros-Lozano, González-Cantó, Mc Cormack, Arrés, Castaño, Cana, Martínez-Fernández, Santonja, Ramírez, Herreros-Pomares, Cañete-Mota, Llueca, Marí-Alexandre, Medina and Gilabert-Estellés.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Sarai Tomás-Pérez (S)

Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain.

Julia Oto (J)

Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain.

Cristina Aghababyan (C)

Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain.
Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain.

Raquel Herranz (R)

Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain.

Aitor Cuadros-Lozano (A)

Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain.
Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain.

Eva González-Cantó (E)

Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain.

Bárbara Mc Cormack (B)

Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain.

Judith Arrés (J)

Department of Statistics and Operational Research, University of Valencia, Valencia, Spain.

María Castaño (M)

Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain.

Fernando Cana (F)

Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain.

Laura Martínez-Fernández (L)

Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain.
Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain.

Núria Santonja (N)

Department of Pathology, General University Hospital of Valencia Consortium, Valencia, Spain.

Rocío Ramírez (R)

Department of Medical Oncology, General University Hospital of Valencia Consortium, Valencia, Spain.

Alejandro Herreros-Pomares (A)

Department of Biotechnology, Polytechnic University of Valencia, Valencia, Spain.
Cancer Biomedical Research Network Center, CIBERONC, Madrid, Spain.

Sarai Cañete-Mota (S)

Department of Obstetrics and Gynecology, General University Hospital of Castellon, Castellón, Spain.

Antoni Llueca (A)

Department of Obstetrics and Gynecology, General University Hospital of Castellon, Castellón, Spain.
Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery (MUAPOS), General University Hospital of Castellon, Castellón, Spain.
Department of Medicine, University Jaume I, Castellón, Spain.

Josep Marí-Alexandre (J)

Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain.
Department of Pathology, General University Hospital of Valencia Consortium, Valencia, Spain.

Pilar Medina (P)

Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain.

Juan Gilabert-Estellés (J)

Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain.
Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain.
Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain.

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