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

Garg, Manik ; Couturier, Dominique Laurent ; Nsengimana, Jérémie ; Fonseca, Nuno A. ; Wongchenko, Matthew ; Yan, Yibing ; Lauss, Martin LU ; Jönsson, Göran B. LU ; Newton-Bishop, Julia and Parkinson, Christine , et al. (2021) In Nature Communications 12(1).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
issue
1
article number
1137
publisher
Nature Publishing Group
external identifiers
  • pmid:33602918
  • scopus:85101229989
ISSN
2041-1723
DOI
10.1038/s41467-021-21207-2
language
English
LU publication?
yes
id
9d162b62-45d8-4bfb-9fb1-30cce6a8ba03
date added to LUP
2021-03-08 09:27:30
date last changed
2024-06-14 10:51:40
@article{9d162b62-45d8-4bfb-9fb1-30cce6a8ba03,
  abstract     = {{<p>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<sup>−5</sup>) and overall survival (HR = 1.61, p = 1.67 × 10<sup>−4</sup>), 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 (p<sub>AUROC</sub> = 7.03 × 10<sup>−4</sup>), or published prognostic signatures (p<sub>AUROC</sub> &lt; 0.05). The signature score negatively correlated with measures of immune cell infiltration (ρ = −0.75, p &lt; 2.2 × 10<sup>−16</sup>), 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.</p>}},
  author       = {{Garg, Manik and Couturier, Dominique Laurent and Nsengimana, Jérémie and Fonseca, Nuno A. and Wongchenko, Matthew and Yan, Yibing and Lauss, Martin and Jönsson, Göran B. and Newton-Bishop, Julia and Parkinson, Christine and Middleton, Mark R. and Bishop, D. Timothy and McDonald, Sarah and Stefanos, Nikki and Tadross, John and Vergara, Ismael A. and Lo, Serigne and Newell, Felicity and Wilmott, James S. and Thompson, John F. and Long, Georgina V. and Scolyer, Richard A. and Corrie, Pippa and Adams, David J. and Brazma, Alvis and Rabbie, Roy}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Tumour gene expression signature in primary melanoma predicts long-term outcomes}},
  url          = {{http://dx.doi.org/10.1038/s41467-021-21207-2}},
  doi          = {{10.1038/s41467-021-21207-2}},
  volume       = {{12}},
  year         = {{2021}},
}