PB0731 - Neutrophil activation markers as novel biomarkers for advanced stages of high-grade serous ovarian cancer

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Julia Oto

Postdoctoral Researcher
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Co-Author(s)

BM

Barbara Mc Cormack

Postdoctoral Researcher
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
ST

Sarai Tomas-Perez

PhD Student
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
AF

Alvaro Fernández-Pardo

Researcher
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe
Valencia, Comunidad Valenciana, Spain
EG

Eva Gonzalez-Canto

PhD Student
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
FC

Fernando Cana

Researcher
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe
Valencia, Comunidad Valenciana, Spain
CA

Cristina Aghababyan

Medical doctor
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
Valencia, Comunidad Valenciana, Spain
Raquel Herranz, MSc

PhD Candidate
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
SC

Sarai Cañete-Mota

Medical doctor
Department of Obstetrics and Gynecology, General University Hospital of Castellon, Castellón, Spain
Castellon, Comunidad Valenciana, Spain
AC

Aitor Cuadros-Lozano

Medical doctor
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
Valencia, Comunidad Valenciana, Spain
LM

Laura Martinez-Fernandez

Medical doctor
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
Valencia, Comunidad Valenciana, Spain
AA

Adrián Aranda-Borreda

Researcher
Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia
Valencia, Comunidad Valenciana, Spain
AA

Adrián Arroyo-Álvarez

Researcher
Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia
Valencia, Comunidad Valenciana, Spain
NS

Nuria Santonja

Medical doctor. PhD
Department of Pathology, General University Hospital of Valencia Consortium, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
RR

Rocio Ramirez

Medical doctor
Department of Medical Oncology, General University Hospital of Valencia Consortium, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
AL

Antoni Llueca

Medical doctor. PhD
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; Department of Medicine, University Jaume I, Castellón, Spain
Castellon, Comunidad Valenciana, Spain
JM

Josep Mari-Alexandre

Postdoctoral Researcher. Medical doctor
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
Valencia, Comunidad Valenciana, Spain
JG

Juan Gilabert-Estelles

Medical doctor
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
Valencia, Comunidad Valenciana, Spain
PM

Pilar Medina

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

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.