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Nevertheless, alterations in the bladder urothelial carcinoma (BLCA) N-glycome remain poorly characterized. Here, we used in situ N-deglycosylation and mass spectrometry, revealing a marked enrichment of oligomannose-type N-glycans in non-invasive Ta tumors, which diminished with disease progression. A complementary analysis of The Cancer Genome Atlas (TCGA) transcriptomic data revealed downregulation of the key mannosidases in BLCA, suggesting a mechanistic basis for oligomannose accumulation, though this requires further validation. Then, targeted glycoproteomic profiling identified potential stage-specific carriers of oligomannoses. Exploratory functional annotation suggests stage-dependent differences among detected glycoproteins, ranging from metabolic regulation in Ta tumors to oxidative stress adaptation in muscle-invasive disease, highlighting glycosylation\u2019s contribution to tumor progression. Furthermore, myeloperoxidase (MPO) was enriched in more aggressive stages. Spatial validation confirmed MPO overexpression in tumor-infiltrating immune cells and its correlation with oligomannose content. Importantly, high MPO expression combined with low mannosidase levels was linked to poor survival, suggesting biological relevance. This study suggests a dynamic, stage-specific N-glycome in BLCA and identifies oligomannose-bearing glycoproteins as exploratory leads for biomarker and therapeutic target discovery, providing a N-glycomic resource for further investigation towards glycan-based precision oncology.<\/jats:p>","DOI":"10.3390\/ijms26104891","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:10:46Z","timestamp":1747721446000},"page":"4891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Glycomics and Glycoproteomics Reveal Distinct Oligomannose Carriers Across Bladder Cancer Stages"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-5414","authenticated-orcid":false,"given":"Marta","family":"Relvas-Santos","sequence":"first","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)\/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-513 Porto, Portugal"},{"name":"LAQV-REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9224-0121","authenticated-orcid":false,"given":"Dylan","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)\/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-513 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences, Fernando Pessoa University, 4420-096 Gondomar, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0938-1543","authenticated-orcid":false,"given":"Andreia","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, Research Center of IPO Porto (CI-IPOP)\/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal"}]},{"given":"Luis Pedro","family":"Afonso","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)\/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal"}]},{"given":"L\u00facio Lara","family":"Santos","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)\/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences, Fernando Pessoa University, 4420-096 Gondomar, Portugal"},{"name":"Department of Surgical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072 Porto, Portugal"},{"name":"GlycoMatters Biotech, 4500-162 Espinho, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-7714","authenticated-orcid":false,"given":"Andr\u00e9 M. N.","family":"Silva","sequence":"additional","affiliation":[{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-513 Porto, Portugal"},{"name":"LAQV-REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"},{"name":"GlycoMatters Biotech, 4500-162 Espinho, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0097-6148","authenticated-orcid":false,"given":"Jos\u00e9 Alexandre","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)\/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-513 Porto, Portugal"},{"name":"GlycoMatters Biotech, 4500-162 Espinho, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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