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Ulcerated melanoma: Systems biology evidence of inflammatory imbalance towards pro-tumourigenicity

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.

Publication metadata

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.


DOI: 10.1111/pcmr.13023


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Funder referenceFunder name
Wellcome Trust