Single cell coagulomes as constituents of the oncogene-driven coagulant phenotype in brain tumours

      Highlights

      • Glioblastma (GBM) illustrates the link between oncogenic driver events and coagulant phenotypes of cancer cells.
      • GBM molecular subtypes differ with respect to expression coagulation-related genes including tissue factor and podoplanin.
      • Emerging evidence links oncogenic driver events with the risk of thrombosis in cancer patients.
      • Single cell sequencing reveals unique coagulomes of individual cancer cells, forming a combinatorial coagulant phenotype.

      Abstract

      Molecular profiling of human cancers revealed a startling diversity in disease-causing mechanisms superseding histological and anatomical commonalities. The emerging molecular subtypes and disease entities are often driven by distinct oncogenic pathways and their effectors, including those acting extracellularly on the vascular and coagulation systems. Indeed, several oncogenic mutations such as those affecting protein-coding genes (RAS, EGFR, PTEN, TP53) and non-coding RNA (microRNA) regulate multiple effectors of the coagulation system (coagulome), including tissue factor, protease activated receptors, clotting factors, mediators of platelet function and fibrinolysis. This is exemplified by differential coagulome profiles in the molecular subtypes of glioblastoma, medulloblastoma and other human tumours. There is mounting clinical evidence that the mutational status of cancer driver genes such as KRAS or IDH1 may influence the risk of venous thromboembolism in patients with colorectal, lung or brain cancers. Notably, single cell sequencing in glioblastoma revealed a remarkable intra-tumoural heterogeneity of cancer cell populations with regard to their individual coagulomes, suggesting a combinatorial and dynamic nature of the global pro-thrombotic phenotype. We suggest that the cellular complexity of specific cancers may define their mechanisms of interactions with the coagulation system, and the risks of thrombosis. Thus, more biologically- based, disease-specific and personalized approaches may be needed to diagnose and manage cancer-related thrombosis.

      Graphical abstract

      Keywords

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