ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Single-Cell Transcriptomic Landscape Deciphers Intratumoral Heterogeneity and Subtypes of Acral and Mucosal Melanomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Preclinical and Virtual Models of Mucosal Melanoma: Bridging Translational Gaps in a Rare and Lethal Cancer.Pigment cell & melanoma research · 2026Review
- Developing a melanoma-skin-on-a-chip integrated with vasculature using an edgeless skin reconstruction approach.Research square · 2026Article
- Lipid metabolism-related molecular typing and prognostic characteristics of cutaneous melanoma.Translational cancer research · 2026Article
- Advanced Mucosal Melanoma Therapies: Current Status and Future Directions.Current treatment options in oncology · 2026Review
- Identification of a lactylation-related gene signature in microsatellite stable gastric cancer based on bulk and single-cell RNA-seq.Frontiers in immunology · 2026Article
- Gradient responsive regularization: a deep learning framework for codon frequency based classification of evolutionarily conserved genes.BMC genomic data · 2025Article
- Integrating Single-Cell and Bulk RNA Sequencing Reveals the Malignant Phenotype of CBX4 in Prostate Cancer.Journal of Cancer · 2025Article
- Targeting Microbe-Mediated Macrophage Education: A Novel Paradigm in Cancer Immunotherapy.Biomaterials research · 2025Review
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Authors and funding
28 authors.
Funding
Abstract
purposeTo identify the specific intratumoral and microenvironmental heterogeneity of acral melanoma (AM) and mucosal melanoma (MM), we aimed to delineate their distinct cellular compositions, evolutionary trajectories, and subtype-specific therapeutic strategies. EXPERIMENTAL
designSingle-cell transcriptomic and genomic landscapes were analyzed across 42 melanoma (28 AM, 11 MM, and 3 nonacral cutaneous melanoma) samples, supplemented by in vitro and in vivo validation. Tumor and stromal cells were profiled using single-cell RNA sequencing, whole-exome sequencing, and functional assays, including transwell migration, co-culture systems, and xenograft models.
resultsTumor cells exhibited divergent evolutionary routes, with MM dominated by MGP+/PCOLCE+ subpopulations showing high epithelial-to-mesenchymal transition potential. MM displayed elevated neutrophil infiltration and CXCL3+ tumor-associated macrophages, whereas AM was enriched with PI16+ cancer-associated fibroblasts promoting tumor proliferation. Molecular classification revealed MM subtypes: an antigen-presenting subtype linked to favorable outcomes and a proliferative subtype associated with recurrence. TIGIT+ regulatory T cells were enriched in AM, suggesting targeted inhibition potential. Genomic analysis connected BRAF/NRAS mutations to ALDOA+ stem-like tumor cells and identified prostaglandin D2 synthetase as a therapeutic target in triple-wild-type/melanomas.
conclusionsOur study provides a comprehensive comparison of AM and MM, uncovering subtype-specific stromal-immune interactions and molecular programs. The findings highlight actionable targets (e.g., TIGIT in AM and CXCL3+ macrophages in MM) and propose a framework for precision therapies, biomarker-driven trials, and risk stratification to improve outcomes in these aggressive melanomas.
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