Abstract
BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy with a strong tendency to metastasize. The prognosis is poor once metastasis occurs. The treatment remains challenging for metastatic UM, even though our understanding of UM has advanced, mostly because the complexity of the genetic and immunologic background has not been fully explored. METHODS: Single-cell sequencing data were acquired from a healthy dataset and three UM datasets. The differentially expressed genes between primary and metastatic UM in The Cancer Genome Atlas (TCGA) data were attributed to specific cell types and explained with functional annotation. The analysis for cell-cell communication was conducted by "CellChat" to understand the cell crosstalk among the cell clusters and to delineate the dysfunctional signaling pathways in metastatic UM. CCK-8, EdU and transwell assays were performed to verify the function of the genes of interest. RESULTS: We revealed aberrant signaling pathways with distinct functional statuses between primary and metastatic UM by integrating multiple datasets. The crucial signals contributing most to outgoing or incoming signaling of metastasis were identified to uncover the potential targeting genes. The association of these genes with disease risk was estimated based on survival data from TCGA. The key genes associated with proliferation and metastasis were verified. CONCLUSIONS: Conclusively, we discovered the potential key signals for occurrence and metastasis of UM and provided a theoretical basis for potential clinical application.