Comprehensive integrated single-cell RNA sequencing analysis of brain metastasis and glioma microenvironment: Contrasting heterogeneity landscapes.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Brain Neoplasms*/secondary ; Brain Neoplasms*/genetics ; Brain Neoplasms*/pathology ; Tumor Microenvironment*/genetics ; Single-Cell Analysis*/methods ; Glioma*/genetics ; Glioma*/pathology ; Sequence Analysis, RNA*; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Lung Neoplasms/secondary ; Female ; Gene Expression Regulation, Neoplastic ; Gene Expression Profiling ; Breast Neoplasms/pathology ; Breast Neoplasms/genetics

Understanding the specific type of brain malignancy, source of brain metastasis, and underlying transformation mechanisms can help provide better treatment and less harm to patients. The tumor microenvironment plays a fundamental role in cancer progression and affects both primary and metastatic cancers. The use of single-cell RNA sequencing to gain insights into the heterogeneity profiles in the microenvironment of brain malignancies is useful for guiding treatment decisions. To comprehensively investigate the heterogeneity in gliomas and brain metastasis originating from different sources (lung and breast), we integrated data from three groups of single-cell RNA-sequencing datasets obtained from GEO. We gathered and processed single-cell RNA sequencing data from 90,168 cells obtained from 17 patients. We then employed the R package Seurat for dataset integration. Next, we clustered the data within the UMAP space and acquired differentially expressed genes for cell categorization. Our results underscore the significance of macrophages as abundant and pivotal constituents of gliomas. In contrast, lung-to-brain metastases exhibit elevated numbers of AT2, cytotoxic CD4+ T, and exhausted CD8+ T cells. Conversely, breast-to-brain metastases are characterized by an abundance of epithelial and myCAF cells. Our study not only illuminates the variation in the TME between brain metastasis with different origins but also opens the door to utilizing established markers for these cell types to differentiate primary brain metastatic cancers.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Sajjadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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Date Created: 20240726 Date Completed: 20240727 Latest Revision: 20240728

20240728

PMC11280140

10.1371/journal.pone.0306220

39058687