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Item Primary and Metastatic Cutaneous Melanomas Discriminately Enrich Several Ligand-Receptor Interactions(MDPI, 2023-01-08) Diaz, Michael J.; Fadil, Angela; Tran, Jasmine T.; Batchu, Sai; Root, Kevin T.; Tran, Andrew X.; Lucke-Wold, Brandon; Dermatology, School of MedicineIntroduction: Cutaneous melanoma remains a leading cancer with sobering post-metastasis mortality rates. To date, the ligand-receptor interactome of melanomas remains weakly studied despite applicability to anti-cancer drug discovery. Here we leverage established crosstalk methodologies to characterize important ligand-receptor pairs in primary and metastatic cutaneous melanoma. Methods: Bulk transcriptomic data, representing 470 cutaneous melanoma samples, was retrieved from the Broad Genome Data Analysis Center Firehose portal. Tumor and stroma compartments were computationally derived as a function of tumor purity estimates. Identification of preferential ligand-receptor interactions was achieved by relative crosstalk scoring of 1380 previously established pairs. Results: Metastatic cutaneous melanoma uniquely enriched PTH2-PTH1R for tumor-to-stroma signaling. The Human R-spondin ligand family was involved in 4 of the 15 top-scoring stroma-to-tumor interactions. Receptor ACVR2B was involved in 3 of the 15 top-scoring tumor-to-tumor interactions. Conclusions: Numerous gene-level differences in ligand-receptor crosstalk between primary and metastatic cutaneous melanomas. Further investigation of notable pairings is warranted.