ArticleESMO open2023
Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases.
Article in ESMO open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Downregulated lysyl oxidase in plasma extracellular vesicles: a biomarker linked to brain metastasis risk in lung adenocarcinoma.BMC medicine · 2026Article
- Classification of driver and passenger mutations in different cancer types using deep neural networks.Bioinformatics advances · 2026Article
- Metabolic adaptations of brain metastasis.Nature reviews. Cancer · 2025Review
- Ghrelin-induced neuronal NPY promotes brain metastasis in lung cancer patients with low BMI.Nature communications · 2025Article
- Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines.Acta neuropathologica communications · 2025Article
- Prediction of brain metastasis development with DNA methylation signatures.Nature medicine · 2025Article
- Review
- What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years.World journal of clinical oncology · 2024Article
- Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2024Review
- Proteomic analyses identify HK1 and ATP5A to be overexpressed in distant metastases of lung adenocarcinomas compared to matched primary tumors.Scientific reports · 2023Article
- Bottom-Up Proteomics: Advancements in Sample Preparation.International journal of molecular sciences · 2023Review
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Authors and funding
24 authors at 11 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBrain metastases are associated with considerable negative effects on patients' outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases. MATERIALS AND
methodsProteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259.
resultsOut of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases.
conclusionsThis is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.
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