Tumor gene expression is associated with venous thromboembolism in patients with ductal pancreatic adenocarcinoma

Abstract

Introduction: In patients with pancreatic cancer, the risk of venous thromboembolism (VTE) is high compared to other cancer types, suggesting that tumor-intrinsic features drive hypercoagulability. Tumor gene expression analysis may help unravel the pathogenesis of VTE in these patients and help to identify high-risk patients. Aim: To evaluate the association between tumor gene expression patterns and VTE in patients with pancreatic cancer. Methods: In this retrospective cohort study RNA-sequence data from surgically resected tumor material from patients with pancreatic ductal adenocarcinoma (PDAC) was used to identify genes associated with the presence of venous thromboembolism (i.e., pulmonary embolism or deep-vein thrombosis) within one year follow-up after surgery. Additionally, VTE risk and expression of coagulation related genes in two molecular subtypes of pancreatic cancer was assessed. Results: Out of 151 patients, 10 (6.6 %) developed deep-vein thrombosis or pulmonary embolism within one year follow-up. Differential expression analysis yielded 89 genes significantly differentially expressed in patients with VTE compared to those without VTE, including ATP6V0A4, SYT14 and ZNF114. The incidence of VTE in classical subtype was higher (n = 9; 7.6 %) than in basal-like subtype (n = 1;4 %), but this difference was not statistically significant (SHR 1.79; 95 % CI 0.22–14.3). Forty-two coagulation-associated genes were identified that were differentially expressed between these molecular subtypes, including F5, PLAU, SERPINE1, and C4BPB. Conclusions: Patients with pancreatic cancer and VTE show a different tumor gene expression profile than those without VTE. Multiple coagulation-related genes were differentially expressed in classical versus basal-like molecular subtype, suggesting that there is a difference in pro-thrombotic phenotype.