Inflammatory breast cancer microenvironment repertoire based on DNA methylation data deconvolution reveals actionable targets to enhance the treatment efficacy

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversity Hospital of Southern Denmark-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorPio XII Foundation-
Autor(es): dc.contributorSENAI CIMATEC-
Autor(es): dc.contributorFederal University of Ceará-
Autor(es): dc.contributorFIOCRUZ-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorCancer Institute of the State of São Paulo (ICESP)-
Autor(es): dc.contributorUniversity of Southern Denmark-
Autor(es): dc.creatorCalanca, Naiade-
Autor(es): dc.creatorFaldoni, Flavia Lima Costa-
Autor(es): dc.creatorSouza, Cristiano Pádua-
Autor(es): dc.creatorSouza, Jeferson Santos-
Autor(es): dc.creatorde Souza Alves, Bianca Elen-
Autor(es): dc.creatorSoares, Milena Botelho Pereira-
Autor(es): dc.creatorWong, Deysi Viviana Tenazoa-
Autor(es): dc.creatorLima-Junior, Roberto César Pereira-
Autor(es): dc.creatorMarchi, Fabio Albuquerque-
Autor(es): dc.creatorRainho, Claudia Aparecida-
Autor(es): dc.creatorRogatto, Silvia Regina-
Data de aceite: dc.date.accessioned2025-08-21T21:10:09Z-
Data de disponibilização: dc.date.available2025-08-21T21:10:09Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1186/s12967-024-05553-5-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/300276-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/300276-
Descrição: dc.descriptionBackground: Although the clinical signs of inflammatory breast cancer (IBC) resemble acute inflammation, the role played by infiltrating immune and stromal cells in this aggressive disease is uncharted. The tumor microenvironment (TME) presents molecular alterations, such as epimutations, prior to morphological abnormalities. These changes affect the distribution and the intricate communication between the TME components related to cancer prognosis and therapy response. Herein, we explored the global DNA methylation profile of IBC and surrounding tissues to estimate the microenvironment cellular composition and identify epigenetically dysregulated markers. Methods: We used the HiTIMED algorithm to deconvolve the bulk DNA methylation data of 24 IBC and six surrounding non-tumoral tissues (SNT) (GSE238092) and determine their cellular composition. The prognostic relevance of cell types infiltrating IBC and their relationship with clinicopathological variables were investigated. CD34 (endothelial cell marker) and CD68 (macrophage marker) immunofluorescence staining was evaluated in an independent set of 17 IBC and 16 non-IBC samples. Results: We found lower infiltration of endothelial, stromal, memory B, dendritic, and natural killer cells in IBC than in SNT samples. Higher endothelial cell (EC) and stromal cell content were related to better overall survival. EC proportions positively correlated with memory B and memory CD8+ T infiltration in IBC. Immune and EC markers exhibited distinct DNA methylation profiles between IBC and SNT samples, revealing hypermethylated regions mapped to six genes (CD40, CD34, EMCN, HLA-G, PDPN, and TEK). We identified significantly higher CD34 and CD68 protein expression in IBC compared to non-IBC. Conclusions: Our findings underscored cell subsets that distinguished patients with better survival and dysregulated markers potentially actionable through combinations of immunotherapy and epigenetic drugs.-
Descrição: dc.descriptionKlinisk Institut, Syddansk Universitet-
Descrição: dc.descriptionSyddansk Universitet-
Descrição: dc.descriptionDepartment of Clinical Genetics University Hospital of Southern Denmark, Beriderbakken 4, DK-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP), SP-
Descrição: dc.descriptionMedical Oncology Department Barretos Cancer Hospital Pio XII Foundation, SP-
Descrição: dc.descriptionHealth Technology Institute SENAI CIMATEC, BA-
Descrição: dc.descriptionDepartment of Physiology and Pharmacology Drug Research and Development Center (NPDM) Faculty of Medicine Federal University of Ceará-
Descrição: dc.descriptionGonçalo Moniz Institute FIOCRUZ, BA-
Descrição: dc.descriptionDepartment of Head and Neck Surgery University of São Paulo Medical School, SP-
Descrição: dc.descriptionCenter for Translational Research in Oncology Cancer Institute of the State of São Paulo (ICESP), SP-
Descrição: dc.descriptionInstitute of Regional Health Research University of Southern Denmark-
Descrição: dc.descriptionBotucatu Medical School Hospital São Paulo State University (UNESP), SP-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP), SP-
Descrição: dc.descriptionBotucatu Medical School Hospital São Paulo State University (UNESP), SP-
Idioma: dc.languageen-
Relação: dc.relationJournal of Translational Medicine-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectDeconvolution-
Palavras-chave: dc.subjectDNA methylation-
Palavras-chave: dc.subjectEndothelial cells-
Palavras-chave: dc.subjectEpigenetic silencing-
Palavras-chave: dc.subjectImmune markers-
Palavras-chave: dc.subjectInflammatory breast cancer-
Palavras-chave: dc.subjectTumor microenvironment-
Título: dc.titleInflammatory breast cancer microenvironment repertoire based on DNA methylation data deconvolution reveals actionable targets to enhance the treatment efficacy-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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