ArticleNeuro-oncology2023
Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 68 citations in OpenAlex.
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- Neuro-immune crosstalk in lung cancer brain metastasis: mechanisms, therapeutic targets, and translational opportunities.Medical oncology (Northwood, London, England) · 2026Review
- [Tumor Cell and Brain Microenvironment Interactions in Non-small Cell Lung Cancer Brain Metastasis: Mechanisms and Emerging Insights].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Machine learning-based prognostic model and single-cell transcriptomic integration for identifying brain metastasis-associated malignant subpopulations and potential therapeutic targets in lung adenocarcinoma.Cancer cell international · 2026Article
- Inhibition of ferroptosis via SLC25A39-NRF2 axis drives Osimertinib resistance in lung adenocarcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- Microbiome-host interactions in different pathomic subtypes of early-stage lung adenocarcinoma.BMC pulmonary medicine · 2026Article
- Integrative spatiotemporal transcriptomics identifies a liver metastasis-related initial cell population associated with the SEMA3A-NRP1 axis in pancreatic ductal adenocarcinoma.Journal of translational medicine · 2026Article
- Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Meningioma microenvironment harbors a rich immune landscape that evolves with biological state.Neuro-oncology · 2026Article
- Integrating AI-driven single-cell analysis to decode epithelial heterogeneity: A prognostic signature and translational immunotherapy strategy targetingChinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Mitotic spindle-organizing protein 2A (MZT2A) promotes cisplatin resistance through NEMO ubiquitination and NF-κB activation in lung adenocarcinoma.The Journal of biological chemistry · 2026Article
- Cellular landscape and diagnostic value of TROP2 in cerebrospinal fluid of lung adenocarcinoma leptomeningeal metastases.NPJ precision oncology · 2026Article
- Downregulated lysyl oxidase in plasma extracellular vesicles: a biomarker linked to brain metastasis risk in lung adenocarcinoma.BMC medicine · 2026Article
- Clinical and immunological significance of tertiary lymphoid structure maturation heterogeneity in brain metastases of lung adenocarcinoma.Journal of translational medicine · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance.Frontiers in cell and developmental biology · 2026Article
- The Spatiotemporal Heterogeneity of Tumor-Associated Stromal Cells: Reprogramming Plasticity to Unlock Precision Cancer Immunotherapy.Cancer communications (London, England) · 2026Review
- USP33 Promotes Lung Adenocarcinoma Brain Metastasis by Inhibiting the K48-Linked Ubiquitination and Degradation of S100A9 and Facilitating Vimentin Secretion.International journal of biological sciences · 2026Article
- A machine learning-derived hypoxia- and lactylation-associated gene signature for prognostic stratification and immune landscape characterization in lung adenocarcinoma.Frontiers in immunology · 2026Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBrain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined.
methodsThe cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate the cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data indicating a high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines.
resultsDifferences in macrophages and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and their biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital. We further evaluated the clinical significance of the BM-index and identified 7 drugs that potentially target BMAECs.
conclusionsThis study clarified possible cellular origins and drivers of metastatic LUAD at the single-cell level and laid a foundation for early detection of LUAD patients with a high risk of BM.
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