Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: Potential role in disease diagnosis and management
IntroductionHigh-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 de...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1111344/full |
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| author | Sarai Tomás-Pérez Julia Oto Cristina Aghababyan Cristina Aghababyan Raquel Herranz Aitor Cuadros-Lozano Aitor Cuadros-Lozano Eva González-Cantó Bárbara Mc Cormack Judith Arrés María Castaño Fernando Cana Laura Martínez-Fernández Laura Martínez-Fernández Núria Santonja Rocío Ramírez Alejandro Herreros-Pomares Alejandro Herreros-Pomares Sarai Cañete-Mota Antoni Llueca Antoni Llueca Antoni Llueca Josep Marí-Alexandre Josep Marí-Alexandre Pilar Medina Juan Gilabert-Estellés Juan Gilabert-Estellés Juan Gilabert-Estellés |
| author_facet | Sarai Tomás-Pérez Julia Oto Cristina Aghababyan Cristina Aghababyan Raquel Herranz Aitor Cuadros-Lozano Aitor Cuadros-Lozano Eva González-Cantó Bárbara Mc Cormack Judith Arrés María Castaño Fernando Cana Laura Martínez-Fernández Laura Martínez-Fernández Núria Santonja Rocío Ramírez Alejandro Herreros-Pomares Alejandro Herreros-Pomares Sarai Cañete-Mota Antoni Llueca Antoni Llueca Antoni Llueca Josep Marí-Alexandre Josep Marí-Alexandre Pilar Medina Juan Gilabert-Estellés Juan Gilabert-Estellés Juan Gilabert-Estellés |
| author_sort | Sarai Tomás-Pérez |
| collection | DOAJ |
| description | IntroductionHigh-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. MethodsSpecifically, 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).ResultsOur 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).DiscussionIn 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. |
| first_indexed | 2024-04-10T17:43:11Z |
| format | Article |
| id | doaj.art-5eb04140b3b74ad2bd9490ac83319c98 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T17:43:11Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5eb04140b3b74ad2bd9490ac83319c982023-02-03T06:52:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11113441111344Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: Potential role in disease diagnosis and managementSarai Tomás-Pérez0Julia Oto1Cristina Aghababyan2Cristina Aghababyan3Raquel Herranz4Aitor Cuadros-Lozano5Aitor Cuadros-Lozano6Eva González-Cantó7Bárbara Mc Cormack8Judith Arrés9María Castaño10Fernando Cana11Laura Martínez-Fernández12Laura Martínez-Fernández13Núria Santonja14Rocío Ramírez15Alejandro Herreros-Pomares16Alejandro Herreros-Pomares17Sarai Cañete-Mota18Antoni Llueca19Antoni Llueca20Antoni Llueca21Josep Marí-Alexandre22Josep Marí-Alexandre23Pilar Medina24Juan Gilabert-Estellés25Juan Gilabert-Estellés26Juan Gilabert-Estellés27Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, SpainHemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, SpainDepartment of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, SpainHemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, SpainDepartment of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, SpainDepartment of Statistics and Operational Research, University of Valencia, Valencia, SpainHemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, SpainHemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, SpainDepartment of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, SpainDepartment of Pathology, General University Hospital of Valencia Consortium, Valencia, SpainDepartment of Medical Oncology, General University Hospital of Valencia Consortium, Valencia, SpainDepartment of Biotechnology, Polytechnic University of Valencia, Valencia, SpainCancer Biomedical Research Network Center, CIBERONC, Madrid, SpainDepartment of Obstetrics and Gynecology, General University Hospital of Castellon, Castellón, SpainDepartment of Obstetrics and Gynecology, General University Hospital of Castellon, Castellón, Spain0Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery (MUAPOS), General University Hospital of Castellon, Castellón, Spain1Department of Medicine, University Jaume I, Castellón, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, SpainDepartment of Pathology, General University Hospital of Valencia Consortium, Valencia, SpainHemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, SpainResearch Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, SpainDepartment of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain2Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, SpainIntroductionHigh-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. MethodsSpecifically, 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).ResultsOur 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).DiscussionIn 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. https://www.frontiersin.org/articles/10.3389/fimmu.2023.1111344/fullhigh-grade serous ovarian cancerbiomarkersNETosiscfDNAcalprotectinperitoneal fluid |
| spellingShingle | Sarai Tomás-Pérez Julia Oto Cristina Aghababyan Cristina Aghababyan Raquel Herranz Aitor Cuadros-Lozano Aitor Cuadros-Lozano Eva González-Cantó Bárbara Mc Cormack Judith Arrés María Castaño Fernando Cana Laura Martínez-Fernández Laura Martínez-Fernández Núria Santonja Rocío Ramírez Alejandro Herreros-Pomares Alejandro Herreros-Pomares Sarai Cañete-Mota Antoni Llueca Antoni Llueca Antoni Llueca Josep Marí-Alexandre Josep Marí-Alexandre Pilar Medina Juan Gilabert-Estellés Juan Gilabert-Estellés Juan Gilabert-Estellés Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: Potential role in disease diagnosis and management Frontiers in Immunology high-grade serous ovarian cancer biomarkers NETosis cfDNA calprotectin peritoneal fluid |
| title | Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: Potential role in disease diagnosis and management |
| title_full | Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: Potential role in disease diagnosis and management |
| title_fullStr | Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: Potential role in disease diagnosis and management |
| title_full_unstemmed | Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: Potential role in disease diagnosis and management |
| title_short | Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: Potential role in disease diagnosis and management |
| title_sort | increased levels of netosis biomarkers in high grade serous ovarian cancer patients biofluids potential role in disease diagnosis and management |
| topic | high-grade serous ovarian cancer biomarkers NETosis cfDNA calprotectin peritoneal fluid |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1111344/full |
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