Ulcerated melanoma: Systems biology evidence of inflammatory imbalance toward pro-tumorigenicity

Simple item page
dc.contributor.authorDavies, John
dc.contributor.authorMuralidhar, Sathya
dc.contributor.authorRanderson-Moor, Juliette
dc.contributor.authorHarland, Mark
dc.contributor.authorO'Shea, Sally
dc.contributor.authorDiaz, Joey
dc.contributor.authorWalker, Christy
dc.contributor.authorNsengimana, Jérémie
dc.contributor.authorLaye, Jon
dc.contributor.authorMell, Tracey
dc.contributor.authorChan, May
dc.contributor.authorAppleton, Lizzie
dc.contributor.authorBirkeälv, Sofia
dc.contributor.authorAdams, David J.
dc.contributor.authorCook, Graham P.
dc.contributor.authorBall, Graham
dc.contributor.authorBishop, D. Timothy
dc.contributor.authorNewton-Bishop, Julia A.
dc.contributor.funderCancer Research UKen
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderHorizon 2020en
dc.contributor.funderMedical Research Councilen
dc.contributor.funderWellcome Trusten
dc.contributor.funderWorldwide Cancer Researchen
dc.date.accessioned2021-12-02T14:14:06Z
dc.date.available2021-12-02T14:14:06Z
dc.date.issued2021-11-26
dc.date.updated2021-12-02T12:52:09Z
dc.description.abstractMicroscopic 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.en
dc.description.sponsorshipCancer Research UK (C588/A19167; C8216/A6129) and and National Institutes of Health (CA83115); Medical Research Council (Project Grant MR/M019012/1) Worldwide Cancer Research (Grant 12-0023)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDavies, 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.13023en
dc.identifier.doi10.1111/pcmr.13023en
dc.identifier.eissn1755-148X
dc.identifier.issn1755-1471
dc.identifier.journaltitlePigment Cell and Melanoma Researchen
dc.identifier.urihttps://hdl.handle.net/10468/12301
dc.language.isoenen
dc.publisherJohn Wiley & Sons, Inc.en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-ITN-ETN/641458/EU/MELanoma GENetics - understanding and biomarking the genetic and immunological determinants of melanoma survival/MELGENen
dc.rights© 2021 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectTranscriptomicsen
dc.subjectCopy numberen
dc.subjectCirculating inflammatory markersen
dc.subjectSmokingen
dc.titleUlcerated melanoma: Systems biology evidence of inflammatory imbalance toward pro-tumorigenicityen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 5 of 5
Thumbnail Image
Name:
Ulcerated melanoma_ Systems biology evidence of inflammatory imbalance towards pro‐tumourigenicity.mhtml
Size:
709.62 KB
Format:
Adobe Portable Document Format
Description:
Published version
Download
Thumbnail Image
Name:
pcmr.13023.pdf
Size:
16.69 MB
Format:
Adobe Portable Document Format
Description:
Accepted Version
Thumbnail Image
Name:
pcmr13023-sup-0001-supinfo.docx
Size:
1.5 MB
Format:
Microsoft Word XML
Description:
Supplementary Material
Download
Thumbnail Image
Name:
pcmr13023-sup-0002-supinfo.xlsx
Size:
14.95 KB
Format:
Microsoft Excel XML
Description:
Supplementary Material
Download
Thumbnail Image
Name:
pcmr13023-sup-0003-supinfo.xlsx
Size:
15.96 KB
Format:
Microsoft Excel XML
Description:
Supplementary Material
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Medicine - Journal Articles