Differential biomarker profiles between unprovoked venous thromboembolism and cancer

Abstract

Background: The relationship between cancer and venous thromboembolic disease (VTD) are complex because the activated coagulation factors are not only involved in thrombosis but also in malignant processes, such as angiogenesis and metastasis. Objective: To compare phenotypes of extracellular vesicles (EVs), and levels of D-dimer, soluble P-selectin (sP-selectin) and antigenic tissue factor (TF) between unprovoked VTD patients, who did not develop cancer during one-year follow-up, and those with advanced stage of cancer but not associated with VTD. Methods: A prospective study in which we included 138 unprovoked VTD patients and 67 advanced cancer patients, who did not develop thrombosis. Levels of EVs of different cellular origin (platelet, endothelium and leukocyte), EVs positive for tissue factor (TF) and P-selectin glycoprotein ligand 1 were quantified by flow cytometry. D-dimer, soluble P-selectin (sP-selectin) and antigenic TF were determined by ELISA. Results: TF-positive EVs, D-dimer, and sP-selectin were markedly elevated in unprovoked VTD patients compared to cancer patients without association with thrombosis. Conclusions: Levels of TF-positive EVs, D-dimer and sP-selectin are able to discriminate between unprovoked VTD patients not related to cancer and cancer patients not associated with VTD. These results could lead to the application of EVs as biomarkers of both diseases. Key messages: Circulating EVs, specifically TF-positive EVs, in combination with plasmatic markers of hypercoagulable states, such as D-dimer, sP-selectin and antigen TF, are able to discriminate between cancer patients without thrombosis and patients with unprovoked VTD. Research fields could be opened. Future studies will assess if these biomarkers together serve as predicting thrombotic events in cancer populations

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

“…P-selectin may play a predictive role in the diagnosis of DVT in cancer patients, according to other researchers [ 26 ]. In venous thrombosis, higher levels of sP-sel were discovered than in advanced-stage cancer patients, leading to the hypothesis that, despite an increase in sP-sel in patients with metastatic cancer, their values rise in acute DVT [ 27 ]. Thrombotic consumptive diseases, such as disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and heparin-induced thrombocytopenia, also have higher levels of P-selectin [ 28 , 29 , 30 ].…”

Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study

“…Numerous techniques are used to determine EVs, including atomic force microscopy, 36 nanotracking analysis, 37 dynamic light scattering, 38 and flow cytometry. 39 , 40 A commonly preferred method for EV quantification is flow cytometry 21 , 41-43 because of its ability to detect, quantify, and characterize EVs simultaneously. Furthermore, flow cytometry is widely available and relatively cost-effective.…”

“…Total EVs, EVs expressing TF on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) were quantified using a BD LSR II flow cytometer (BD Biosciences), as previously described by our group, with minor modifications. 20 , 21 In brief, a total of 30 µL of PPP was thawed and incubated at a temperature range of 20 to 25 °C for 30 minutes in the dark. This incubation was carried out with the following specific monoclonal antibodies: mouse anti-human CD142-FITC (clone VD8, product No.…”

Nanoparticles of a New Small-Molecule P-Selectin Inhibitor Attenuate Thrombosis, Inflammation, and Tumor Growth in Two Animal Models

“…It is evident that inhibiting the binding between P-selectin and PSGL1 sheds light on drug development for treating inflammation, 5 arterial thrombosis, 6 venous thrombosis, 7 tumor growth, 8 tumor metastasis, 8 and cancer-associated thrombosis. [9][10][11] Currently, drugs designed for this purpose mainly fall into three types: monoclonal antibodies, including inclacumab 12 and crizanlizumab, 13 glycosulfopeptides mimicking truncated N-terminal PSGL1 monomers like GSnP-6, 14 and small-molecule inhibitors, such as GMI-1070, 15 bimosiamose (TBC1269), 16 and PSI-697. 17 Those drugs, however, are far from satisfying for clinical use.…”

“…It is evident that inhibiting the binding between P-selectin and PSGL1 sheds light on drug development for treating inflammation, 5 arterial thrombosis, 6 venous thrombosis, 7 tumor growth, 8 tumor metastasis, 8 and cancer-associated thrombosis. 9–11 …”