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Genomic subtypes of cutaneous melanoma have distinct metabolic profiles: A single-cell transcriptomic analysis

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Abstract

Objective

Genomic profiling previously classified melanoma into distinct subtypes based on the presence or absence of mutations in driver genes, but metabolic differences between and within these groups have yet to be thoroughly analyzed. Thus, the objective of the present study is to provide the first effort to holistically characterize the metabolic landscape of qualified melanoma genomic subtypes at single-cell resolution.

Methods

Expression data for a total of 1145 malignant cells sourced from NRAS(Q61L), BRAF(V600E), and NRAS/BRAF WT melanomas were retrieved from the Broad Single Cell Portal. Metabolic activity was interrogated by pathway scoring and gene set enrichment analysis.

Results

A total of 53 metabolic pathways were differentially regulated in at least one melanoma genomic subtype. Some notable findings include: BRAF/NRAS WT cells were enriched for fatty acid biosynthesis and depleted for metabolism of alanine, aspartate, and glutamate; BRAF(V600E) melanoma cells were enriched for beta-alanine metabolism and depleted for phenylalanine metabolism; NRAS(Q61L) melanoma cells were enriched for steroid biosynthesis and depleted for linoleic acid metabolism.

Conclusion

Primary limitations include the total quantity of single cells and breadth of available genomic subtypes plus inherent noisiness of the applied methodologies. Nonetheless, these findings nominate novel, testable therapeutic targets.

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Fig. 1

Abbreviations

scRNA:

Single-cell RNA sequencing

TPM:

Transcripts per million

UMAP:

Uniform Manifold Approximation and Projection

PCA:

Principal component analysis

GSEA:

Gene set enrichment analysis

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Acknowledgements

None.

Funding

The present study had no funding source.

Author information

Authors and Affiliations

  1. College of Medicine, University of Florida, Gainesville, FL, USA

    Michael J. Diaz, Kevin T. Root, Silvija Milanovic & Angela Fadil

  2. School of Medicine, Indiana University, Indianapolis, IN, USA

    Jasmine T. Tran

  3. Medical College, Weill Cornell Medicine, New York, NY, USA

    Zi-Ning Choo

  4. Cooper Medical School, Rowan University, Camden, NJ, USA

    Sai Batchu

  5. Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Lauren Ladehoff

  6. Department of Dermatology, Weill Cornell Medicine, New York, NY, USA

    Shari R. Lipner

Authors
  1. Michael J. Diaz
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  2. Jasmine T. Tran
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  4. Kevin T. Root
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  5. Sai Batchu
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  6. Silvija Milanovic
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  7. Lauren Ladehoff
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  8. Angela Fadil
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  9. Shari R. Lipner
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Contributions

MJD: Conceptualization, Methodology, Writing—Original draft preparation, Writing—Review & Editing, Software, Data curation, Validation.: JTT: Conceptualization, Methodology, Writing—Original draft preparation.: Z-NC: Methodology, Validation, Writing—Review & Editing.: KTR: Validation, Writing—Original draft preparation, Writing—Review & Editing.: SB: Methodology, Software.: SM: Writing—Original draft preparation, Writing—Review & Editing.: LL: Writing—Original draft preparation, Writing—Review & Editing.: AF: Writing—Original draft preparation.: SRL: Writing—Review & Editing, Supervision.

Corresponding author

Correspondence to Michael J. Diaz.

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Conflict of interest

Dr. Shari Lipner has served as a consultant for Ortho-dermatologics, Hoth Therapeutics, Moberg Pharmaceuticals and BelleTorus Corporation.

Ethical approval

The present study is exempt from IRB approval requirements.

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Diaz, M.J., Tran, J.T., Choo, ZN. et al. Genomic subtypes of cutaneous melanoma have distinct metabolic profiles: A single-cell transcriptomic analysis. Arch Dermatol Res 315, 2961–2965 (2023). https://doi.org/10.1007/s00403-023-02690-7

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  • DOI: https://doi.org/10.1007/s00403-023-02690-7

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