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  • Garg, ManikEuropean Bioinformatics Institute (author)

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

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-02-18
  • Springer Science and Business Media LLC,2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:9d162b62-45d8-4bfb-9fb1-30cce6a8ba03
  • https://lup.lub.lu.se/record/9d162b62-45d8-4bfb-9fb1-30cce6a8ba03URI
  • https://doi.org/10.1038/s41467-021-21207-2DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Couturier, Dominique LaurentUniversity of Cambridge (author)
  • Nsengimana, JérémieUniversity of Newcastle upon Tyne,University of Leeds (author)
  • Fonseca, Nuno A.University of Porto (author)
  • Wongchenko, MatthewGenentech, Inc (author)
  • Yan, YibingGenentech, Inc (author)
  • Lauss, MartinLund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)med-mlu (author)
  • Jönsson, Göran B.Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-gjo (author)
  • Newton-Bishop, JuliaUniversity of Leeds (author)
  • Parkinson, ChristineCambridge University Hospitals NHS Foundation Trust (author)
  • Middleton, Mark R.University of Oxford (author)
  • Bishop, D. TimothyUniversity of Leeds (author)
  • McDonald, SarahCambridge University Hospitals NHS Foundation Trust (author)
  • Stefanos, NikkiCambridge University Hospitals NHS Foundation Trust (author)
  • Tadross, JohnCambridge University Hospitals NHS Foundation Trust (author)
  • Vergara, Ismael A.University of Sydney (author)
  • Lo, SerigneImam Abdulrahman Bin Faisal University,University of Sydney (author)
  • Newell, FelicityQIMR Berghofer Medical Research Institute (author)
  • Wilmott, James S.University of Sydney (author)
  • Thompson, John F.University of Sydney (author)
  • Long, Georgina V.University of Sydney,Royal North Shore Hospital (author)
  • Scolyer, Richard A.University of Sydney,Royal Prince Alfred Hospital (author)
  • Corrie, PippaCambridge University Hospitals NHS Foundation Trust (author)
  • Adams, David J.Wellcome Trust Sanger Institute (author)
  • Brazma, AlvisEuropean Bioinformatics Institute (author)
  • Rabbie, RoyWellcome Trust Sanger Institute,Cambridge University Hospitals NHS Foundation Trust (author)
  • European Bioinformatics InstituteUniversity of Cambridge (creator_code:org_t)

Related titles

  • In:Nature Communications: Springer Science and Business Media LLC12:12041-1723

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