Gene signature reveals decreased SOX10-dependent transcripts in malignant cells from immune checkpoint inhibitor-resistant cutaneous melanomas.
Cancer systems biology
Classification Description
Molecular network
Omics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
15 Sep 2023
15 Sep 2023
Historique:
received:
16
02
2023
revised:
18
06
2023
accepted:
21
07
2023
medline:
28
8
2023
pubmed:
28
8
2023
entrez:
28
8
2023
Statut:
epublish
Résumé
Evidence is mounting for cross-resistance between immune checkpoint and targeted kinase inhibitor therapies in cutaneous melanoma patients. Since the loss of the transcription factor, SOX10, causes tolerance to MAPK pathway inhibitors, we used bioinformatic techniques to determine if reduced SOX10 expression/activity is associated with immune checkpoint inhibitor resistance. We integrated SOX10 ChIP-seq, knockout RNA-seq, and knockdown ATAC-seq data from melanoma cell models to develop a robust SOX10 gene signature. We used computational methods to validate this signature as a measure of SOX10-dependent activity in independent single-cell and bulk RNA-seq SOX10 knockdown, cell line panel, and MAPK inhibitor drug-resistant datasets. Evaluation of patient single-cell RNA-seq data revealed lower levels of SOX10-dependent transcripts in immune checkpoint inhibitor-resistant tumors. Our results suggest that SOX10-deficient melanoma cells are associated with cross-resistance between targeted and immune checkpoint inhibitors and highlight the need to identify therapeutic strategies that target this subpopulation.
Identifiants
pubmed: 37636077
doi: 10.1016/j.isci.2023.107472
pii: S2589-0042(23)01549-3
pmc: PMC10450419
doi:
Banques de données
figshare
['10.6084/m9.figshare.11791698.v3']
Types de publication
Journal Article
Langues
eng
Pagination
107472Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
A.E. Aplin has ownership interest in patent number 9880150 and has a pending patent, PCT/US22/76492.
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