Abstract C47: Plasma ANP and soluble cell adhesion molecule X are novel risk factors for pancreatic cancer-associated thrombosis

Abstract

Cancer-associated thrombosis/thromboembolism (CAT) is a serious clinical complication and leads to occasional cause of death in patients with cancers, including pancreatic ductal adenocarcinoma (PDAC). However, diagnostic and inhibitory approach for CAT is still unestablished. We found that CAT with cardiomegaly and increase of plasma atrial natriuretic peptide (ANP) were frequently observed in the PDAC mice containing conditional KrasG12D mutation and knockout of TGF-β receptor type II (Tgfbr2) (PKF mice). Similar to usual thrombotic patients without cancer, high plasma level of cytokines including soluble cell adhesion molecule X was detected in the mice. Molecule-X was immunohistochemically observed in activated endothelium and thrombi. Injection of neutralized anti-molecule-X antibody reduced onset of CAT and cardiac weight in the PKF mice. Meanwhile, high plasma levels of ANP and/or molecule-X were detected in PDAC patients before and after diagnosis of CAT. Taken together, increase of ANP and/or molecule-X is a new risk factor of CAT in PDAC patients. Blocking molecule-X, at least in part, would be an inhibitory approach for CAT in PDAC. Citation Format: Makoto Sano, Hideaki Ijichi, Kazunaga Ishigaki, Ryota Takahashi, Koji Miyabayashi, Keisuke Tateishi, Hiroyuki Isayama, Kazuhiko Koike. Plasma ANP and soluble cell adhesion molecule X are novel risk factors for pancreatic cancer-associated thrombosis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C47.