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

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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; Jönsson, Göran B.; Newton-Bishop, Julia; Parkinson, Christine; Middleton, Mark R.; Bishop, D. Timothy; McDonald, Sarah; Stefanos, Nikki; Tadross, John; Vergara, Ismael A.; Lo, Serigne; Newell, Felicity; Wilmott, James S.; Thompson, John F.; Long, Georgina V.; Scolyer, Richard A.; Corrie, Pippa; Adams, David J.; Brazma, Alvis; Rabbie, Roy.

In: Nature Communications, Vol. 12, No. 1, 1137, 2021.

Research output: Contribution to journalArticle

Harvard

Garg, M, Couturier, DL, Nsengimana, J, Fonseca, NA, Wongchenko, M, Yan, Y, Lauss, M, Jönsson, GB, Newton-Bishop, J, Parkinson, C, Middleton, MR, Bishop, DT, McDonald, S, Stefanos, N, Tadross, J, Vergara, IA, Lo, S, Newell, F, Wilmott, JS, Thompson, JF, Long, GV, Scolyer, RA, Corrie, P, Adams, DJ, Brazma, A & Rabbie, R 2021, 'Tumour gene expression signature in primary melanoma predicts long-term outcomes', Nature Communications, vol. 12, no. 1, 1137. https://doi.org/10.1038/s41467-021-21207-2

APA

Garg, M., Couturier, D. L., Nsengimana, J., Fonseca, N. A., Wongchenko, M., Yan, Y., Lauss, M., Jönsson, G. B., Newton-Bishop, J., Parkinson, C., Middleton, M. R., Bishop, D. T., McDonald, S., Stefanos, N., Tadross, J., Vergara, I. A., Lo, S., Newell, F., Wilmott, J. S., ... Rabbie, R. (2021). Tumour gene expression signature in primary melanoma predicts long-term outcomes. Nature Communications, 12(1), [1137]. https://doi.org/10.1038/s41467-021-21207-2

CBE

Garg M, Couturier DL, Nsengimana J, Fonseca NA, Wongchenko M, Yan Y, Lauss M, Jönsson GB, Newton-Bishop J, Parkinson C, Middleton MR, Bishop DT, McDonald S, Stefanos N, Tadross J, Vergara IA, Lo S, Newell F, Wilmott JS, Thompson JF, Long GV, Scolyer RA, Corrie P, Adams DJ, Brazma A, Rabbie R. 2021. Tumour gene expression signature in primary melanoma predicts long-term outcomes. Nature Communications. 12(1):Article 1137. https://doi.org/10.1038/s41467-021-21207-2

MLA

Vancouver

Garg M, Couturier DL, Nsengimana J, Fonseca NA, Wongchenko M, Yan Y et al. Tumour gene expression signature in primary melanoma predicts long-term outcomes. Nature Communications. 2021;12(1). 1137. https://doi.org/10.1038/s41467-021-21207-2

Author

Garg, Manik ; Couturier, Dominique Laurent ; Nsengimana, Jérémie ; Fonseca, Nuno A. ; Wongchenko, Matthew ; Yan, Yibing ; Lauss, Martin ; Jönsson, Göran B. ; Newton-Bishop, Julia ; Parkinson, Christine ; Middleton, Mark R. ; Bishop, D. Timothy ; McDonald, Sarah ; Stefanos, Nikki ; Tadross, John ; Vergara, Ismael A. ; Lo, Serigne ; Newell, Felicity ; Wilmott, James S. ; Thompson, John F. ; Long, Georgina V. ; Scolyer, Richard A. ; Corrie, Pippa ; Adams, David J. ; Brazma, Alvis ; Rabbie, Roy. / Tumour gene expression signature in primary melanoma predicts long-term outcomes. In: Nature Communications. 2021 ; Vol. 12, No. 1.

RIS

TY - JOUR

T1 - Tumour gene expression signature in primary melanoma predicts long-term outcomes

AU - Garg, Manik

AU - Couturier, Dominique Laurent

AU - Nsengimana, Jérémie

AU - Fonseca, Nuno A.

AU - Wongchenko, Matthew

AU - Yan, Yibing

AU - Lauss, Martin

AU - Jönsson, Göran B.

AU - Newton-Bishop, Julia

AU - Parkinson, Christine

AU - Middleton, Mark R.

AU - Bishop, D. Timothy

AU - McDonald, Sarah

AU - Stefanos, Nikki

AU - Tadross, John

AU - Vergara, Ismael A.

AU - Lo, Serigne

AU - Newell, Felicity

AU - Wilmott, James S.

AU - Thompson, John F.

AU - Long, Georgina V.

AU - Scolyer, Richard A.

AU - Corrie, Pippa

AU - Adams, David J.

AU - Brazma, Alvis

AU - Rabbie, Roy

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-21207-2

DO - 10.1038/s41467-021-21207-2

M3 - Article

C2 - 33602918

AN - SCOPUS:85101229989

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1137

ER -