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Clin Exp Med ; 24(1): 187, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136841

RESUMO

Glioblastoma (GBM) is a highly heterogeneous disease with poor clinical outcomes. To comprehensively dissect the molecular landscape of GBM and heterogeneous macrophage clusters in the progression of GBM, this study integrates single-cell and bulk transcriptome data to recognize a distinct pro-tumor macrophage cluster significantly associated with the prognosis of GBM and develop a GBM prognostic signature to facilitate prior subtypes. Leveraging glioma single-cell sequencing data, we identified a novel pro-tumor macrophage subgroup, marked by S100A9, which might interact with endothelial cells to facilitate tumor progression via angiogenesis. To further benefit clinical application, a prognostic signature was established with the genes associated with pro-tumor macrophages. Patients classified within the high-risk group characterized with enrichment in functions related to tumor progression, including epithelial-mesenchymal transition and hypoxia, displays elevated mutations in the TERT promoter region, reduced methylation in the MGMT promoter region, poorer prognoses, and diminished responses to temozolomide therapy, thus effectively discriminating between the prognostic outcomes of GBM patients. Our research sheds light on the intricate microenvironment of gliomas and identifies potential molecular targets for the development of novel therapeutic approaches.


Assuntos
Perfilação da Expressão Gênica , Glioblastoma , Análise de Célula Única , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Microambiente Tumoral/genética , Temozolomida/uso terapêutico , Macrófagos/metabolismo , Transcriptoma , Telomerase/genética , Proteínas Supressoras de Tumor/genética , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA
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