Tumour gene expression signature in primary melanoma predicts long-term outcomes

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dc.contributor.authorGarg, Manik
dc.contributor.authorCouturier, Dominique-Laurent
dc.contributor.authorNsengimana, Jérémie
dc.contributor.authorFonseca, Nuno A.
dc.contributor.authorWongchenko, Matthew
dc.contributor.authorYan, Yibing
dc.contributor.authorLauss, Martin
dc.contributor.authorJönsson, Göran B.
dc.contributor.authorNewton-Bishop, Julia
dc.contributor.authorParkinson, Christine
dc.contributor.authorMiddleton, Mark R.
dc.contributor.authorBishop, D. Timothy
dc.contributor.authorMcDonald, Sarah
dc.contributor.authorStefanos, Nikki
dc.contributor.authorTadross, John
dc.contributor.authorVergara, Ismael A.
dc.contributor.authorLo, Serigne
dc.contributor.authorNewell, Felicity
dc.contributor.authorWilmott, James S.
dc.contributor.authorThompson, John F.
dc.contributor.authorLong, Georgina V.
dc.contributor.authorScolyer, Richard A.
dc.contributor.authorCorrie, Pippa
dc.contributor.authorAdams, David J.
dc.contributor.authorBrazma, Alvis
dc.contributor.authorRabbie, Roy
dc.contributor.orcidGarg, Manik [0000-0003-0453-2058]
dc.contributor.orcidCouturier, Dominique-Laurent [0000-0001-5774-5036]
dc.contributor.orcidNsengimana, Jérémie [0000-0002-3603-4208]
dc.contributor.orcidFonseca, Nuno A. [0000-0003-4832-578X]
dc.contributor.orcidWongchenko, Matthew [0000-0003-1230-7117]
dc.contributor.orcidMiddleton, Mark R. [0000-0003-0167-1685]
dc.contributor.orcidBishop, D. Timothy [0000-0002-8752-8785]
dc.contributor.orcidTadross, John [0000-0002-8424-1252]
dc.contributor.orcidVergara, Ismael A. [0000-0002-2960-2967]
dc.contributor.orcidLo, Serigne [0000-0001-5092-5544]
dc.contributor.orcidNewell, Felicity [0000-0003-0469-2705]
dc.contributor.orcidThompson, John F. [0000-0002-2816-2496]
dc.contributor.orcidScolyer, Richard A. [0000-0002-8991-0013]
dc.contributor.orcidAdams, David J. [0000-0001-9490-0306]
dc.contributor.orcidBrazma, Alvis [0000-0001-5988-7409]
dc.contributor.orcidRabbie, Roy [0000-0002-9195-5659]
dc.date.accessioned2022-05-17T15:00:42Z
dc.date.available2022-05-17T15:00:42Z
dc.date.issued2021-02-18
dc.date.submitted2020-03-10
dc.date.updated2022-05-17T15:00:41Z
dc.descriptionFunder: University of Sydney Medical Foundation
dc.descriptionFunder: Department of Health | National Health and Medical Research Council (NHMRC); doi: https://doi.org/10.13039/501100000925
dc.description.abstractAbstract: Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We use differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR = 1.63, p = 5.24 × 10−5) and overall survival (HR = 1.61, p = 1.67 × 10−4), was validated in 175 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC = 7.03 × 10−4), or published prognostic signatures (pAUROC < 0.05). The signature score negatively correlated with measures of immune cell infiltration (ρ = −0.75, p < 2.2 × 10−16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.
dc.identifier.doi10.17863/CAM.84661
dc.identifier.eissn2041-1723
dc.identifier.others41467-021-21207-2
dc.identifier.other21207
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337245
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/67/69
dc.subject/631/67/1813/1634
dc.subject/631/67/1857
dc.subject/45/91
dc.subject/38/39
dc.subject/38/90
dc.subject/141
dc.subjectarticle
dc.titleTumour gene expression signature in primary melanoma predicts long-term outcomes
dc.typeArticle
dcterms.dateAccepted2021-01-15
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume12
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-021-21207-2
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