Comprehensive Analysis of Lung Adenocarcinoma and Brain Metastasis through Integrated Single-Cell Transcriptomics

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorBritish Columbia Cancer Research Institute-
Autor(es): dc.contributorBritish Columbia Children’s Hospital Research Institute-
Autor(es): dc.creatorSouza, Vanessa G. P.-
Autor(es): dc.creatorTelkar, Nikita-
Autor(es): dc.creatorLam, Wan L.-
Autor(es): dc.creatorReis, Patricia P.-
Data de aceite: dc.date.accessioned2025-08-21T19:50:46Z-
Data de disponibilização: dc.date.available2025-08-21T19:50:46Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-04-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/ijms25073779-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/302310-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/302310-
Descrição: dc.descriptionLung adenocarcinoma (LUAD) is a highly prevalent and lethal form of lung cancer, comprising approximately half of all cases. It is often diagnosed at advanced stages with brain metastasis (BM), resulting in high mortality rates. Current BM management involves complex interventions and conventional therapies that offer limited survival benefits with neurotoxic side effects. The tumor microenvironment (TME) is a complex system where cancer cells interact with various elements, significantly influencing tumor behavior. Immunotherapies, particularly immune checkpoint inhibitors, target the TME for cancer treatment. Despite their effectiveness, it is crucial to understand metastatic lung cancer and the specific characteristics of the TME, including cell–cell communication mechanisms, to refine treatments. Herein, we investigated the tumor microenvironment of brain metastasis from lung adenocarcinoma (LUAD-BM) and primary tumors across various stages (I, II, III, and IV) using single-cell RNA sequencing (scRNA-seq) from publicly available datasets. Our analysis included exploring the immune and non-immune cell composition and the expression profiles and functions of cell type-specific genes, and investigating the interactions between different cells within the TME. Our results showed that T cells constitute the majority of immune cells present in primary tumors, whereas microglia represent the most dominant immune cell type in BM. Interestingly, microglia exhibit a significant increase in the COX pathway. Moreover, we have shown that microglia primarily interact with oligodendrocytes and endothelial cells. One significant interaction was identified between DLL4 and NOTCH4, which demonstrated a relevant association between endothelial cells and microglia and between microglia and oligodendrocytes. Finally, we observed that several genes within the HLA complex are suppressed in BM tissue. Our study reveals the complex molecular and cellular dynamics of BM-LUAD, providing a path for improved patient outcomes with personalized treatments and immunotherapies.-
Descrição: dc.descriptionCanadian Institutes of Health Research-
Descrição: dc.descriptionCanadian HIV Trials Network, Canadian Institutes of Health Research-
Descrição: dc.descriptionLotte and John Hecht Memorial Foundation-
Descrição: dc.descriptionBC Cancer Foundation-
Descrição: dc.descriptionTerry Fox Foundation-
Descrição: dc.descriptionMolecular Oncology Laboratory Experimental Research Unit Faculty of Medicine São Paulo State University (UNESP), SP-
Descrição: dc.descriptionBritish Columbia Cancer Research Institute-
Descrição: dc.descriptionBritish Columbia Children’s Hospital Research Institute-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics Faculty of Medicine São Paulo State University (UNESP), SP-
Descrição: dc.descriptionMolecular Oncology Laboratory Experimental Research Unit Faculty of Medicine São Paulo State University (UNESP), SP-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics Faculty of Medicine São Paulo State University (UNESP), SP-
Descrição: dc.descriptionCanadian Institutes of Health Research: 183775-
Descrição: dc.descriptionCanadian HIV Trials Network, Canadian Institutes of Health Research: 183775-
Descrição: dc.descriptionCanadian Institutes of Health Research: FRN-143345-
Descrição: dc.descriptionCanadian HIV Trials Network, Canadian Institutes of Health Research: FRN-143345-
Idioma: dc.languageen-
Relação: dc.relationInternational Journal of Molecular Sciences-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectbrain metastasis-
Palavras-chave: dc.subjectlung cancer-
Palavras-chave: dc.subjectNSCLC-
Palavras-chave: dc.subjecttumor microenvironment-
Título: dc.titleComprehensive Analysis of Lung Adenocarcinoma and Brain Metastasis through Integrated Single-Cell Transcriptomics-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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