{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zeng J"],"funding":["the Science Foundation of Guangdong Second Provincial General Hospital","Talents' plan Foundation of Guangdong Second Provincial General Hospital","Guangzhou Basic Research Plan Jointly the City, School"],"pagination":["e0336502"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12643271"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(11)"],"pubmed_abstract":["Melanoma brain metastasis (MBM) remains lethal with limited treatment efficacy. Meanwhile, the cellular origins and drivers of brain metastasis from melanoma have yet to be defined. Through integrated single-cell/single-nucleus RNA sequencing of 26 melanoma samples, we identified a pre-brain-metastatic tumor subpopulation (MBMATCs, MBM-associated tumor cells) within a conserved malignant cell trajectory (Mela3). MBMATCs exhibited activated pro-metastatic pathways and upregulated neural/adhesion genes (NRG3, NCAM1), suggesting a cellular origin for brain tropism. MBM ecosystems showed T cell exhaustion (elevated PD-1, HAVCR2, LAG3) and Treg enrichment. An MBM-Index derived from bulk RNA-seq accurately quantifies MBMATCs abundance, independently predicting poor overall survival in both TCGA-SKCM and validation cohorts. Furthermore, we assessed the clinical relevance of the MBM-Index and uncovered five candidate drugs with potential activity against MBMATCs. This study identifies MBMATCs as brain metastasis associated tumor cells and positions the MBM-Index as a biomarker for early stratification of melanoma patients at high risk of brain metastasis."],"journal":["PloS one"],"pubmed_title":["Single-cell transcriptomics profiling reveals cellular origins and molecular drivers underlying melanoma brain metastasis."],"pmcid":["PMC12643271"],"funding_grant_id":["No.2024A03J0483","No.2024B003","No.YQ2020-001"],"pubmed_authors":["Luo Q","Wen J","Huang W","Zeng J","Ma Y","Lin L"],"additional_accession":[]},"is_claimable":false,"name":"Single-cell transcriptomics profiling reveals cellular origins and molecular drivers underlying melanoma brain metastasis.","description":"Melanoma brain metastasis (MBM) remains lethal with limited treatment efficacy. Meanwhile, the cellular origins and drivers of brain metastasis from melanoma have yet to be defined. Through integrated single-cell/single-nucleus RNA sequencing of 26 melanoma samples, we identified a pre-brain-metastatic tumor subpopulation (MBMATCs, MBM-associated tumor cells) within a conserved malignant cell trajectory (Mela3). MBMATCs exhibited activated pro-metastatic pathways and upregulated neural/adhesion genes (NRG3, NCAM1), suggesting a cellular origin for brain tropism. MBM ecosystems showed T cell exhaustion (elevated PD-1, HAVCR2, LAG3) and Treg enrichment. An MBM-Index derived from bulk RNA-seq accurately quantifies MBMATCs abundance, independently predicting poor overall survival in both TCGA-SKCM and validation cohorts. Furthermore, we assessed the clinical relevance of the MBM-Index and uncovered five candidate drugs with potential activity against MBMATCs. This study identifies MBMATCs as brain metastasis associated tumor cells and positions the MBM-Index as a biomarker for early stratification of melanoma patients at high risk of brain metastasis.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025","modification":"2026-05-21T03:12:24.75Z","creation":"2026-05-21T03:10:57.504Z"},"accession":"S-EPMC12643271","cross_references":{"pubmed":["41284647"],"doi":["10.1371/journal.pone.0336502"]}}