The Dynamic Landscape of the Coagulome of Metastatic Malignant Melanoma

The local expression of coagulation-related genes defines the tumor coagulome. The tumor coagulome plays a pivotal role in cancer-associated thrombosis (CAT) and hemostatic complications, such as venous thromboembolism (VTE), which are frequent in patients with advanced/metastatic cancer. Genomic analyses of human tumors, such as skin cutaneous melanoma (SKCM), have unveiled the complexity of the metastatic trajectories. However, no study to date has focused on the metastatic coagulome along these trajectories. Using bulk-tumor and single-cell analyses of primary SKCM, metastastic samples and circulating tumor cells (CTCs), we explored the coagulome of SKCM along metastatic progression. We identified consistent changes in the coagulome of SKCM metastases compared to primary tumors and observed metastatic site specificity. Compared to other metastatic sites, lung metastases of SKCM had a specific coagulome with a higher expression of F3, encoding Tissue Factor. Single-cell analyses were used to chart the inter- and intra-tumor heterogeneity and characterize the metastatic coagulome of SKCM. We found that a subpopulation of CTCs from SKCM expressed high levels of platelet genes, suggesting the contribution of CTC-platelet interactions to the CTC coagulome. These findings highlight the dynamic properties of the metastatic coagulome and its link to cancer progression.