Elevated levels of citrullinated fibrinogen in patients with cancer

Author:

Arfman Tom1ORCID,Zollet Valentina23,van Es Nick45,Bosch Floris T. M.4,Nicolaes Gerry A. F.6,Sorvillo Nicoletta2,Voorberg Jan17ORCID

Affiliation:

1. Department of Molecular Hematology Sanquin Research and Landsteiner Laboratory Amsterdam The Netherlands

2. Department for BioMedical Research (DBMR) University of Bern Bern Switzerland

3. Graduate School for Cellular and Biomedical Sciences (GCB) University of Bern Bern Switzerland

4. Department of Vascular Medicine Amsterdam UMC location University of Amsterdam Amsterdam The Netherlands

5. Amsterdam Cardiovascular Sciences Pulmonary Hypertension and Thrombosis Amsterdam The Netherlands

6. Department of Biochemistry Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Maastricht The Netherlands

7. Department of Experimental Vascular Medicine Academic Medical Centre Amsterdam University of Amsterdam Amsterdam The Netherlands

Abstract

AbstractNeutrophil released peptidyl arginine deiminase 4 (PAD4) converts arginine residues on plasma proteins into citrulline. Here, we developed an assay to quantify citrullinated fibrinogen. We employed a biotin‐conjugated phenylglyoxal (biotin‐phenylglyoxal (PG)) compound that selectively labels citrulline. Patient samples were derived from a multicenter prospective cohort study that aimed to identify cancer patients at high risk for venous thromboembolism (VTE). Our data show that cancer patients have higher (median 2‐fold increased) citrullinated fibrinogen levels when compared to normal human plasma and a cohort of healthy donors. Our results show that citrullination of fibrinogen is a common posttranslational modification in patients with cancer.

Funder

Trombosestichting Nederland

Publisher

Wiley

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