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Lookup NU author(s): Dr Jérémie Nsengimana
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd. Microscopic ulceration is an independent predictor of melanoma death. Here, we used systems biology to query the role of host and tumour-specific processes in defining the phenotype. Albumin level as a measure of systemic inflammation was predictive of fewer tumour-infiltrating lymphocytes and poorer survival in the Leeds Melanoma Cohort. Ulcerated melanomas were thicker and more mitotically active (with corresponding transcriptomic upregulated cell cycle pathways). Sequencing identified tumoural p53 and APC mutations, and TUBB2B amplification as associated with the phenotype. Ulcerated tumours had perturbed expression of cytokine genes, consistent with protumourigenic inflammation and histological and transcriptomic evidence for reduced adaptive immune cell infiltration. Pathway/network analysis of multiomic data using neural networks highlighted a role for the β-catenin pathway in the ulceration, linking genomic changes in the tumour to immunosuppression and cell proliferation. In summary, the data suggest that ulceration is in part associated with genomic changes but that host factors also predict melanoma death with evidence of reduced immune responses to the tumour.
Author(s): 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, Birkealv S, Adams DJ, Cook GP, Ball G, Bishop DT, Newton-Bishop JA
Publication type: Article
Publication status: Published
Journal: Pigment Cell and Melanoma Research
Year: 2022
Volume: 35
Issue: 2
Pages: 252-267
Print publication date: 01/03/2022
Online publication date: 26/11/2021
Acceptance date: 23/11/2021
Date deposited: 12/01/2022
ISSN (print): 1755-1471
ISSN (electronic): 1755-148X
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1111/pcmr.13023
DOI: 10.1111/pcmr.13023
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