Abstract
Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited tools are available to identify high risk patients. Upon activation, neutrophils release their content through different mechanisms, thereby prompting thrombosis. We explored plasma microRNAs (miRNAs) and neutrophil activation markers to predict VTE in pancreatic ductal adenocarcinoma (PDAC) and distal extrahepatic cholangiocarcinoma (DECC). Twenty-six PDAC and 6 DECC patients recruited at cancer diagnosis, were examined for deep vein thrombosis and pulmonary embolisms, and were then followed-up with clinical examinations, blood collections, and biCUS. Ten patients developed VTE and were compared with 22 age- and sex-matched controls. miRNA expression levels were measured at diagnosis and right before VTE, and neutrophil activation markers (cell-free DNA, nucleosomes, calprotectin, and myeloperoxidase) were measured in every sample obtained during follow-up. We obtained a profile of 7 miRNAs able to estimate the risk of future VTE at diagnosis (AUC = 0.95; 95% Confidence Interval (CI) (0.987, 1)) with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. Seven miRNAs were up- or down-regulated before VTE compared with diagnosis. We obtained a predictive model of VTE with calprotectin as predictor (AUC = 0.77; 95% CI (0.57, 0.95)). This is the first study that addresses the ability of plasma miRNAs and neutrophil activation markers to predict VTE in PDAC and DECC.
Highlights
Venous thromboembolism (VTE) is a condition in which blood clots form most often in the deep veins of the leg, known as deep vein thrombosis (DVT)
We aimed to identify up- or down-regulated miRNAs in the sample right before the VTE event compared with that obtained at inclusion, since this could shed light on the mechanism triggering a VTE event in pancreatic ductal adenocarcinoma (PDAC) and distal extrahepatic cholangiocarcinoma (DECC) patients
Applying this predictive model, we estimated the thrombotic risk of each PDAC and DECC patient of our study at inclusion, and the median thrombotic risk of the group of patients who suffered a VTE during follow-up was 0.72, while it was only 0.13 in the group of patients who did not suffer a VTE during follow-up (p < 0.0001), confirming the predictive ability of our model
Summary
Venous thromboembolism (VTE) is a condition in which blood clots form most often in the deep veins of the leg, known as deep vein thrombosis (DVT). When this blood clot is disrupted from the vessel wall, it can travel in the circulation and lodge in the lungs, thereby causing a pulmonary embolism (PE). VTE is associated with a median overall survival of 5.8 months in patients with VTE vs 10.3 months in patients without VTE (p = 0.031). The overall survival is even worse when the VTE event occurs during chemotherapy [5]. Metastatic pancreatic cancer patients have a 2.1-fold higher risk for recurrent VTE than other metastatic cancer patients
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