Levels of Alternatively Spliced Tissue Factor in the Plasma of Patients with Pancreatic Cancer May Help Predict Aggressive Tumor Phenotype

Background. Circulating ('blood-borne') tissue factor (TF) is implicated in the pathogenesis of several chronic conditions, most notably cardiovascular disease, diabetes, and cancer. Full-length TF is an integral membrane protein, while alternatively spliced TF (asTF) can be secreted and, owing to its unique C-terminus, selectively detected in bio-specimens. The predictive and/or prognostic value of asTF in the circulation is unknown. In a retrospective study, we measured levels of circulating asTF in healthy subjects and individuals with acute coronary syndrome (ACS), diabetes mellitus (DM), ongoing ACS + DM, and pancreatic ductal adenocarcinoma (PDAC). Methods. The prototype-tailored procedure (Diagnostica Stago) was used to measure asTF in plasma from 205 subjects. Results. There was no significant difference between the proportion of healthy subjects with asTF >= 200 pg/mL and those with ACS, DM, or ACS ? DM. The proportion of pancreatic cancer patients (n = 43; PDAC: 42; pancreatic neuroendocrine tumor: 1) with asTF levels >= 200 pg/mL was significantly higher than in healthy subjects; asTF levels >= 200 pg/mL were detected more often in patients with unresectable disease irrespective of initial evaluation and/or preoperative carbohydrate antigen 19-9 (CA19-9) levels. Conclusions. While asTF levels >= 200 pg/mL are not observed with increased frequency in patients with ACS and/or DM, they do occur more frequently in the plasma of patients with pancreatic cancer and are associated with lower likelihood of tumor resectability, irrespective of the preoperative diagnosis. asTF may thus have utility as a novel marker of aggressive pancreatic tumor phenotype.