Elevated levels of citrullinated fibrinogen in patients with cancer

Neutrophil 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. Citrullination is a post-translational modification of arginine. Recent research has shown that citrullination can affect the activity of coagulation factors like fibrinogen. Quantitative analysis of citrullinated fibrinogen showed that cancer patients who are at increased risk of developing venous thromboembolism have significantly increased levels of circulating citrullinated fibrinogen compared to healthy controls. This finding is indicative of widespread plasma protein citrullination in cancer patients. image