Association of neutrophil extracellular traps with the production of circulating DNA in patients with colorectal cancer
Brice Pastor,
Jean-Daniel Abraham,
Ekaterina Pisareva,
Cynthia Sanchez,
Andrei Kudriavstev,
Rita Tanos,
Alexia Mirandola,
Lucia Mihalovičová,
Veronique Pezzella,
Antoine Adenis,
Marc Ychou,
Thibault Mazard,
Alain R. Thierry
Affiliations
Brice Pastor
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France
Jean-Daniel Abraham
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France
Ekaterina Pisareva
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France
Cynthia Sanchez
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France
Andrei Kudriavstev
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France
Rita Tanos
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France
Alexia Mirandola
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France
Lucia Mihalovičová
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France; Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava 811 08, Slovakia
Veronique Pezzella
UNICANCER, Paris, France
Antoine Adenis
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France; Department of Medical Oncology, Montpellier Cancer Institute (ICM), Montpellier, France
Marc Ychou
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France; Department of Medical Oncology, Montpellier Cancer Institute (ICM), Montpellier, France
Thibault Mazard
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France; Department of Medical Oncology, Montpellier Cancer Institute (ICM), Montpellier, France
Alain R. Thierry
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France; Department of Medical Oncology, Montpellier Cancer Institute (ICM), Montpellier, France; Corresponding author
Summary: We postulate that a significant part of circulating DNA (cirDNA) originates in the degradation of neutrophil extracellular traps (NETs). In this study, we examined the plasma level of two markers of NETs (myeloperoxidase (MPO) and neutrophil elastase (NE)), as well as cirDNA levels in 219 patients with a metastatic colorectal cancer (mCRC), and in 114 healthy individuals (HI). We found that in patients with mCRC the content of these analytes was (i) highly correlated, and (ii) all statistically different (p < 0.0001) than in HI (N = 114). These three NETs markers may readily distinguish between patients with mCRC from HI, (0.88, 0.86, 0.84, and 0.95 AUC values for NE, MPO, cirDNA, and NE + MPO + cirDNA, respectively). Concomitant analysis of anti-phospholipid (anti-cardiolipin), NE, MPO, and cirDNA plasma concentrations in patients with mCRC might have value for thrombosis prevention, and suggested that NETosis may be a critical factor in the immunological response/phenomena linked to tumor progression.
