Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36527824", "kind": "science-record", "revision": 2, "content_hash": "sha256:58c0b1f1a7177b2606b77dce7b22b49e09b9f54ef091eb07a26000b827d3ab9b", "created_at": "2026-11-01T19:01:02Z", "updated_at": "2026-11-01T21:29:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases.", "doi": "10.1016/j.esmoop.2022.100741", "pmid": "36527824", "authors": ["N Woldmar", "A Schwendenwein", "M Kuras", "B Szeitz", "K Boettiger", "A Tisza", "V László", "L Reiniger", "A G Bagó", "Z Szállási", "J Moldvay", "A M Szász", "J Malm", "P Horvatovich", "L Pizzatti", "G B Domont", "F Rényi-Vámos", "K Hoetzenecker", "M A Hoda", "G Marko-Varga", "K Schelch", "Z Megyesfalvi", "M Rezeli", "B Döme"], "journal": "ESMO open", "year": 2023, "abstract": "BACKGROUND: Brain 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.\nMATERIALS AND METHODS: Proteomic 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.\nRESULTS: Out 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.\nCONCLUSIONS: This 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.", "claims": [{"id": "claim-method", "statement": "In addition, Kaplan–Meier analysis was applied to predict the development of BM using the best cut-off point for each protein from the PRM results (Figure 4C).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36527824", "locator": "sections[10] \"Verification of proteins associated with fast BM development\" paragraph 4", "quote": "In addition, Kaplan–Meier analysis was applied to predict the development of BM using the best cut-off point for each protein from the PRM results (Figure 4C)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE35 partner repository with the data set identifier PXD027259.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36527824", "locator": "sections[4] \"Data availability\" paragraph 2", "quote": "The mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE35 partner repository with the data set identifier PXD027259."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36527824", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36527824"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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