A large pooled analysis refines gene expression-based molecular subclasses in cutaneous melanoma

Thijs T. Wind; Mathilde Jalving; Jacco J. de Haan; Elisabeth G. E. de Vries; Marcel A. T. M. van Vugt; Dirk-Jan Reijngoud; Rozemarijn S. van Rijn; John B. A. G. Haanen; Christian U. Blank; Geke A. P. Hospers; Rudolf S. N. Fehrmann

doi:10.1080/2162402X.2018.1558664

A large pooled analysis refines gene expression-based molecular subclasses in cutaneous melanoma

Thijs T. Wind, Mathilde Jalving, Jacco J. de Haan, Elisabeth G. E. de Vries, Marcel A. T. M. van Vugt, Dirk-Jan Reijngoud, Rozemarijn S. van Rijn, John B. A. G. Haanen, Christian U. Blank, Geke A. P. Hospers, Rudolf S. N. Fehrmann^*

^*Corresponding author for this work

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Abstract

This study aimed to establish the number of expression-based molecular subclasses in cutaneous melanoma, identify their dominant biological pathways and evaluate their clinical relevance. To this end, consensus clustering was performed separately on two independent datasets (n = 405 and n = 473) composed of publicly available cutaneous melanoma expression profiles from previous studies. Four expression-based molecular subclasses were identified and labelled 'Oxidative phosphorylation', 'Oestrogen response/p53-pathway', 'Immune' and 'Cell cycle', based on their dominantly expressed biological pathways determined by gene set enrichment analysis. Multivariate survival analysis revealed shorter overall survival in the 'Oxidative phosphorylation' subclass compared to the other subclasses. This was validated in a third independent dataset (n = 214). Finally, in a pooled cohort of 76 patients treated with anti-PD-1 therapy a trend towards a difference in response rates between subclasses was observed ('Immune' subclass: 65% responders, 'Oxidative Phosphorylation' subclass: 60% responders, other subclasses:

Original language	English
Article number	1558664
Number of pages	11
Journal	OncoImmunology
Volume	8
Issue number	3
DOIs	https://doi.org/10.1080/2162402X.2018.1558664
Publication status	Published - 2019

Keywords

Cutaneous melanoma
gene expression
consensus clustering
pooled analysis
molecular classification
anti-PD-1 therapy
METASTATIC MELANOMA
CELL
METABOLISM
SURVIVAL
CANCER
PGC1-ALPHA
INHIBITOR
THERAPIES
SUBTYPES
CDK4

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Wind, T. T., Jalving, M., de Haan, J. J., de Vries, E. G. E., van Vugt, M. A. T. M., Reijngoud, D.-J., van Rijn, R. S., Haanen, J. B. A. G., Blank, C. U., Hospers, G. A. P., & Fehrmann, R. S. N. (2019). A large pooled analysis refines gene expression-based molecular subclasses in cutaneous melanoma. OncoImmunology, 8(3), Article 1558664. https://doi.org/10.1080/2162402X.2018.1558664

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title = "A large pooled analysis refines gene expression-based molecular subclasses in cutaneous melanoma",

abstract = "This study aimed to establish the number of expression-based molecular subclasses in cutaneous melanoma, identify their dominant biological pathways and evaluate their clinical relevance. To this end, consensus clustering was performed separately on two independent datasets (n = 405 and n = 473) composed of publicly available cutaneous melanoma expression profiles from previous studies. Four expression-based molecular subclasses were identified and labelled 'Oxidative phosphorylation', 'Oestrogen response/p53-pathway', 'Immune' and 'Cell cycle', based on their dominantly expressed biological pathways determined by gene set enrichment analysis. Multivariate survival analysis revealed shorter overall survival in the 'Oxidative phosphorylation' subclass compared to the other subclasses. This was validated in a third independent dataset (n = 214). Finally, in a pooled cohort of 76 patients treated with anti-PD-1 therapy a trend towards a difference in response rates between subclasses was observed ('Immune' subclass: 65% responders, 'Oxidative Phosphorylation' subclass: 60% responders, other subclasses:",

keywords = "Cutaneous melanoma, gene expression, consensus clustering, pooled analysis, molecular classification, anti-PD-1 therapy, METASTATIC MELANOMA, CELL, METABOLISM, SURVIVAL, CANCER, PGC1-ALPHA, INHIBITOR, THERAPIES, SUBTYPES, CDK4",

author = "Wind, {Thijs T.} and Mathilde Jalving and {de Haan}, {Jacco J.} and {de Vries}, {Elisabeth G. E.} and {van Vugt}, {Marcel A. T. M.} and Dirk-Jan Reijngoud and {van Rijn}, {Rozemarijn S.} and Haanen, {John B. A. G.} and Blank, {Christian U.} and Hospers, {Geke A. P.} and Fehrmann, {Rudolf S. N.}",

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doi = "10.1080/2162402X.2018.1558664",

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AU - Wind, Thijs T.

AU - Jalving, Mathilde

AU - de Haan, Jacco J.

AU - de Vries, Elisabeth G. E.

AU - van Vugt, Marcel A. T. M.

AU - Reijngoud, Dirk-Jan

AU - van Rijn, Rozemarijn S.

AU - Haanen, John B. A. G.

AU - Blank, Christian U.

AU - Hospers, Geke A. P.

AU - Fehrmann, Rudolf S. N.

PY - 2019

Y1 - 2019

N2 - This study aimed to establish the number of expression-based molecular subclasses in cutaneous melanoma, identify their dominant biological pathways and evaluate their clinical relevance. To this end, consensus clustering was performed separately on two independent datasets (n = 405 and n = 473) composed of publicly available cutaneous melanoma expression profiles from previous studies. Four expression-based molecular subclasses were identified and labelled 'Oxidative phosphorylation', 'Oestrogen response/p53-pathway', 'Immune' and 'Cell cycle', based on their dominantly expressed biological pathways determined by gene set enrichment analysis. Multivariate survival analysis revealed shorter overall survival in the 'Oxidative phosphorylation' subclass compared to the other subclasses. This was validated in a third independent dataset (n = 214). Finally, in a pooled cohort of 76 patients treated with anti-PD-1 therapy a trend towards a difference in response rates between subclasses was observed ('Immune' subclass: 65% responders, 'Oxidative Phosphorylation' subclass: 60% responders, other subclasses:

AB - This study aimed to establish the number of expression-based molecular subclasses in cutaneous melanoma, identify their dominant biological pathways and evaluate their clinical relevance. To this end, consensus clustering was performed separately on two independent datasets (n = 405 and n = 473) composed of publicly available cutaneous melanoma expression profiles from previous studies. Four expression-based molecular subclasses were identified and labelled 'Oxidative phosphorylation', 'Oestrogen response/p53-pathway', 'Immune' and 'Cell cycle', based on their dominantly expressed biological pathways determined by gene set enrichment analysis. Multivariate survival analysis revealed shorter overall survival in the 'Oxidative phosphorylation' subclass compared to the other subclasses. This was validated in a third independent dataset (n = 214). Finally, in a pooled cohort of 76 patients treated with anti-PD-1 therapy a trend towards a difference in response rates between subclasses was observed ('Immune' subclass: 65% responders, 'Oxidative Phosphorylation' subclass: 60% responders, other subclasses:

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KW - METABOLISM

KW - SURVIVAL

KW - CANCER

KW - PGC1-ALPHA

KW - INHIBITOR

KW - THERAPIES

KW - SUBTYPES

KW - CDK4

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DO - 10.1080/2162402X.2018.1558664

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JO - OncoImmunology

JF - OncoImmunology

IS - 3

M1 - 1558664

ER -

A large pooled analysis refines gene expression-based molecular subclasses in cutaneous melanoma

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Keywords

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