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

Fecha de publicación: 03/02/2023 Fecha Ahead of Print: 03/02/2023

Autores de IIS La Fe

Ana Julia Oto Martínez

Autor
Raquel Herranz Gómez

Autor
María Del Carmen Castaño García

Autor
Fernando Cana Vidal

Autor
Pilar Medina Badenes

Autor

Participantes ajenos a IIS La Fe

Tomás-Pérez S
Aghababyan C
Cuadros-Lozano A
González-Cantó E
Mc Cormack B
Arrés J
Martínez-Fernández L
Santonja N
Ramírez R
Herreros-Pomares A
Cañete-Mota S
Llueca A
Marí-Alexandre J
Gilabert-Estellés J

Grupos

Hemostasia, Trombosis, Arteriosclerosis y Biología vascular

Investigador Principal

Pilar Medina Badenes

Abstract

INTRODUCTION: 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. METHODS: 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). RESULTS: 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). DISCUSSION: 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.

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.

Datos de la publicación

ISSN/ISSNe:: 1664-3224, 1664-3224
Tipo:: Article
Páginas:: 1111344-1111344
DOI:: 10.3389/fimmu.2023.1111344
Factor de Impacto:: 2,331 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Tomás-Pérez S:: Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Oto J:: Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
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
Herranz R:: Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
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
González-Cantó E:: Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Mc Cormack B:: Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Arrés J:: Department of Statistics and Operational Research, University of Valencia, Valencia, Spain
Castaño M:: Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Cana F:: Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
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
Santonja N:: Department of Pathology, General University Hospital of Valencia Consortium, Valencia, Spain
Ramírez R:: Department of Medical Oncology, General University Hospital of Valencia Consortium, Valencia, Spain
Herreros-Pomares A:: Department of Biotechnology, Polytechnic University of Valencia, Valencia, Spain

Cancer Biomedical Research Network Center, CIBERONC, Madrid, Spain
Cañete-Mota S:: Department of Obstetrics and Gynecology, General University Hospital of Castellon, Castellón, Spain
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
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
Medina P:: Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
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

Keywords

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

Proyectos asociados

RED INVESTIGACION (RECAVA)

RD06/0014/0004 . INSTITUTO DE SALUD CARLOS III; FUNDACION PARA LA INV BIOMEDICA- HOSPITAL GREGORIO MARAÑON; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2006