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A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Primary and Metastatic Cutaneous Melanomas Discriminately Enrich Several Ligand-Receptor Interactions
Michael J Diaz1, Angela Fadil1, Jasmine T Tran2
1College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Introduction:
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.
Insights
Cutaneous melanoma progression involves distinct ligand-receptor signaling. This study identified key interactions in metastatic melanoma, offering new targets for anti-cancer drug discovery.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Cutaneous melanoma is a significant cancer with high mortality after metastasis.
- The ligand-receptor interactions in melanoma are not well understood, limiting anti-cancer drug development.
Purpose of the Study:
- To characterize ligand-receptor pairs in primary and metastatic cutaneous melanoma using established crosstalk methodologies.
- To identify unique signaling pathways in metastatic melanoma.
Main Methods:
- Utilized bulk transcriptomic data from 470 cutaneous melanoma samples.
- Computationally derived tumor and stroma compartments.
- Identified ligand-receptor interactions via relative crosstalk scoring of 1380 pairs.
Main Results:
- Metastatic melanoma showed enrichment of PTH2-PTH1R for tumor-to-stroma signaling.
- The Human R-spondin ligand family was prominent in stroma-to-tumor interactions.
- Receptor ACVR2B was involved in tumor-to-tumor interactions.
Conclusions:
- Significant gene-level differences in ligand-receptor crosstalk exist between primary and metastatic melanoma.
- Further research into identified ligand-receptor pairings is recommended for therapeutic strategies.
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