{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:48:06Z","timestamp":1790344086043,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006595","name":"Romanian National Authority for Scientific Research","doi-asserted-by":"publisher","award":["PN-IV-P2-2.1-TE-2023-0175"],"award-info":[{"award-number":["PN-IV-P2-2.1-TE-2023-0175"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Aurel Vlaicu University of Arad","award":["UAV-IRG-1-2025-8"],"award-info":[{"award-number":["UAV-IRG-1-2025-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lung adenocarcinoma (LUAD), the most prevalent subtype of non-small cell lung carcinoma (NSCLC), commonly metastasizes to the brain, particularly in advanced stages. Since brain metastases (BMs) are a leading cause of morbidity and mortality in LUAD patients, their early detection is critical, necessitating the identification of reliable biomarkers. Gangliosides (GGs), a class of bioactive glycosphingolipids involved in cell signaling, adhesion, and immune regulation, have emerged as promising candidates for diagnostic and therapeutic targeting in LUAD-associated brain metastases (BMLA). In this context, ion mobility spectrometry mass spectrometry (IMS-MS) was employed here to analyze GG alterations in BMLA tissues compared to healthy cerebellar control. The results revealed marked differences, including a reduction in the total number of species, altered sialylation profiles, and variations in fatty acid chain length and sphingoid base hydroxylation. GM3, a monosialodihexosylganglioside, was significantly overexpressed in BMLA, supporting its role in tumor progression via immune evasion and oncogenic signaling. Elevated levels of the brain-specific GT1 ganglioside further point to its possible role as a metastasis-associated biomarker, while the presence of asialogangliosides, absent in normal brain, suggests adaptation to the brain microenvironment. Structural modifications such as O-acetylation, fucosylation, and CH3COO\u2212 were more frequent in BMLA, being associated with aggressive tumor phenotypes. Ceramide profiles revealed increased levels of proliferative C16- and C24-ceramides and decreased pro-apoptotic C18-ceramide. Additionally, GM3(d18:1\/22:0) and GD3(d18:1\/16:0), identified as potential BMLA biomarkers, were structurally characterized using (\u2212) nanoelectrospray ionization (nanoESI) IMS collision-induced dissociation tandem MS (CID MS\/MS). Collectively, these findings highlight the clinical potential of GGs for early diagnosis and targeted therapy in BMLA.<\/jats:p>","DOI":"10.3390\/ijms262412029","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Overexpression of GM3 and Ganglioside Pattern Remodeling in Lung Adenocarcinoma Brain Metastases Identified by Ion Mobility Mass Spectrometry"],"prefix":"10.3390","volume":"26","author":[{"given":"Mirela","family":"Sarbu","sequence":"first","affiliation":[{"name":"Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300224 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca","family":"Ica","sequence":"additional","affiliation":[{"name":"Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300224 Timisoara, Romania"},{"name":"Department of Technical and Natural Sciences, \u201cAurel Vlaicu\u201d University of Arad, 310130 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljka","family":"Vukeli\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Clemmer","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The College of Arts & Science, Indiana University, Bloomington, IN 47405-7102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina D.","family":"Zamfir","sequence":"additional","affiliation":[{"name":"Department of Technical and Natural Sciences, \u201cAurel Vlaicu\u201d University of Arad, 310130 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102693","DOI":"10.1016\/j.canep.2024.102693","article-title":"Global Burden of Lung Cancer in 2022 and Projections to 2050: Incidence and Mortality Estimates from GLOBOCAN","volume":"93","author":"Zhou","year":"2024","journal-title":"Cancer Epidemiol."},{"key":"ref_2","first-page":"12","article-title":"Cancer Statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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