Zuzana Saidak1,2, Simon Soudet3, Marine Lottin4, Valéry Salle4, Marie-Antoinette Sevestre5,3, Florian Clatot6,7, Antoine Galmiche8,9. 1. EA7516 CHIMERE, Université de Picardie Jules Verne, Amiens, France. Saidak.Zuzana@chu-amiens.fr. 2. Service d'Oncobiologie Moléculaire, Centre de Biologie Humaine (CBH), CHU Amiens Sud, Avenue Laennec, 80054, Amiens Cedex, France. Saidak.Zuzana@chu-amiens.fr. 3. Service de Médecine Vasculaire, CHU, Amiens, France. 4. Service de Biochimie, Centre de Biologie Humaine (CBH), CHU Amiens Sud, Avenue Laennec, 80054, Amiens Cedex, France. 5. EA7516 CHIMERE, Université de Picardie Jules Verne, Amiens, France. 6. Centre Henri Becquerel, Rouen, France. 7. INSERM U1245/IRON Team, Rouen, France. 8. EA7516 CHIMERE, Université de Picardie Jules Verne, Amiens, France. Galmiche.antoine@chu-amiens.fr. 9. Service de Biochimie, Centre de Biologie Humaine (CBH), CHU Amiens Sud, Avenue Laennec, 80054, Amiens Cedex, France. Galmiche.antoine@chu-amiens.fr.
Abstract
OBJECTIVE: Solid tumors often establish a procoagulable state that can lead to venous thromboembolism (VTE). Although some of the key genes involved in this process are known, no previous study has compared the "coagulome", i.e., the expression of coagulation/fibrinolysis genes, across different primary tumor types. It is also unclear whether the coagulome is associated with specific characteristics of the tumor microenvironment (TME). We aimed to address this question. METHODS: We analyzed the expression of the genes F3, PLAU, PLAT, PLAUR, SERPINB2, and SERPINE1 in 32 cancer types using data from The Cancer Genome Atlas (TCGA) and other freely available resources. RESULTS: We identified specific expression patterns of procoagulant and fibrinolytic genes. The expression of the Tissue Factor (F3) was found to be tumor type dependent, with the highest expression in glioblastoma (GBM), a highly procoagulable tumor type. Conversely, high expression of the fibrinolysis gene cluster PLAU, PLAUR, SERPINE1 was consistently linked to the characteristics of the TME (monocytic infiltration) and high expression of important checkpoints of the immune response, such as PD-L2 and CD276/B7-H3. CONCLUSION: These tumor-specific patterns of expression might partially explain the differences in VTE risk among tumor types. We propose that biomarkers of coagulation fibrinolysis might provide valuable information about the TME in cancer patients.
OBJECTIVE: Solid tumors often establish a procoagulable state that can lead to venous thromboembolism (VTE). Although some of the key genes involved in this process are known, no previous study has compared the "coagulome", i.e., the expression of coagulation/fibrinolysis genes, across different primary tumor types. It is also unclear whether the coagulome is associated with specific characteristics of the tumor microenvironment (TME). We aimed to address this question. METHODS: We analyzed the expression of the genes F3, PLAU, PLAT, PLAUR, SERPINB2, and SERPINE1 in 32 cancer types using data from The Cancer Genome Atlas (TCGA) and other freely available resources. RESULTS: We identified specific expression patterns of procoagulant and fibrinolytic genes. The expression of the Tissue Factor (F3) was found to be tumor type dependent, with the highest expression in glioblastoma (GBM), a highly procoagulable tumor type. Conversely, high expression of the fibrinolysis gene cluster PLAU, PLAUR, SERPINE1 was consistently linked to the characteristics of the TME (monocytic infiltration) and high expression of important checkpoints of the immune response, such as PD-L2 and CD276/B7-H3. CONCLUSION: These tumor-specific patterns of expression might partially explain the differences in VTE risk among tumor types. We propose that biomarkers of coagulation fibrinolysis might provide valuable information about the TME in cancerpatients.
Entities:
Keywords:
Cancer-associated thrombosis; Coagulome; Fibrinolysis; The Cancer Genome Atlas (TCGA); Tissue factor; Tumor microenvironment
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