Ulcerated melanoma: Systems biology evidence of inflammatory imbalance toward pro-tumorigenicity
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Supplementary Material
Supplementary Material
Supplementary Material
Date
2021-11-26
Authors
Davies, John
Muralidhar, Sathya
Randerson-Moor, Juliette
Harland, Mark
O'Shea, Sally
Diaz, Joey
Walker, Christy
Nsengimana, Jérémie
Laye, Jon
Mell, Tracey
Journal Title
Journal ISSN
Volume Title
Publisher
John Wiley & Sons, Inc.
Published Version
Abstract
Microscopic ulceration is an independent predictor of melanoma death. Here we used systems biology to query the role of host and tumor specific processes in defining the phenotype. Measures of systemic inflammation were predictive of fewer tumor infiltrating lymphocytes and poorer survival. Ulcerated melanomas were thicker and more mitotically active (transcriptomic upregulated cell-cycle pathways). Sequencing identified tumoral p53 and APC mutations, and TUBB2B amplification as associated with the phenotype. Ulcerated tumors had perturbed expression of cytokine genes, consistent with protumorigenic inflammation and histological and transcriptomic evidence for reduced adaptive immune cell infiltration. Pathway/network analysis of multi-omic data using neural networks highlighted a role for the à -catenin pathway in the ulceration, linking genomic changes in the tumor to immunosuppression and cell proliferation. In summary the data suggest that ulceration is in part associated with genomic changes but that host factors predict melanoma death with evidence of reduced immune responses to the tumor.
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Keywords
Transcriptomics , Copy number , Circulating inflammatory markers , Smoking
Citation
Davies, J., Muralidhar, S., Randerson-Moor, J., Harland, M., O'Shea, S., Diaz, J., Walker, C., Nsengimana, J., Laye, J., Mell, T., Chan, M., Appleton, L., Birkeälv, S., Adams, D. J., Cook, G. P., Ball, G., Bishop, D. T. and Newton-Bishop, J. A. (2021) 'Ulcerated melanoma: Systems biology evidence of inflammatory imbalance toward pro-tumorigenicity', Pigment Cell and Melanoma Research. doi: 10.1111/pcmr.13023