Unraveling Thromboinflammation Abnormalities in Pancreatic Cancer: Implications for Diagnosis and Treatment

Abstract

Abstract Accumulating evidence suggested a complex interplay between coagulation disorder and inflammation in the progression of pancreatic cancer. Here, blood test results about hematological, biochemical indicators, coagulation assays, rapid thromboelastogram (r-TEG), inflammatory profiles and serum tumor markers were collected to uncover their potential implications for disease pathophysiology and explore reliable predictive parameters in pancreatic cancer (PC). A cohort of 109 PC and 91 controls were enrolled. Patients with PC exhibited a pro-coagulant state with shortened kinetics time (K), and an increased in alpha angle (Angle), maximum amplitude (MA), clot strength (G), prothrombin time (PT), plasma fibrinogen (FIB) and D-dimer (P < 0.001). Significantly elevated Interleukin 6 (IL6) levels indicated a pro-inflammatory microenvironment in PC. Correlation analyses revealed significant associations among pro-coagulant, pro-inflammatory, and pro-tumorigenic factors. Cluster analysis was employed to recognize thrombosis or inflammation phenotypes. We found that tumor necrosis factor-alpha (TNF-alpha) was significantly high in hypercoagulation subgroup of PC (P < 0.01). Meanwhile, FIB, D-dimer, PT and international normalized ratio (INR) were significantly high in hyper-inflammation subset characterized with high IL-6. Moreover, machine learning methods demonstrated excellent predictive performance of coagulation-related models for PC. This study provides insights into the complex pathophysiological landscape of PC, emphasizing the interplay between coagulation, inflammation, and tumor progression.