{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:20:33Z","timestamp":1792668033746,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U54 DK130065"],"award-info":[{"award-number":["U54 DK130065"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01 CA196387"],"award-info":[{"award-number":["U01 CA196387"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21 CA276896"],"award-info":[{"award-number":["R21 CA276896"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21 CA256271"],"award-info":[{"award-number":["R21 CA256271"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01 CA226051"],"award-info":[{"award-number":["U01 CA226051"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Approximately 300,000 American men were diagnosed with prostate cancer in 2024. Existing screening approaches based on measuring levels of prostate-specific antigen in the blood lack specificity for prostate cancer. Studying the glycans attached to proteins has the potential to generate new biomarker candidates and\/or increase the specificity of existing protein biomarkers, and studying protein glycosylation changes in prostate cancer could also add new information to our understanding of prostate cancer biology. Here, we present the analysis of N-glycoproteins in clinical prostate cancer tissue and patient-matched, non-cancerous adjacent tissue using LC\u2013MS\/MS-based intact N-linked glycopeptide analysis. This analysis allowed us to characterize protein N-linked glycosylation changes in prostate cancer at the glycoprotein, glycopeptide, and glycosite levels. Overall, 1894 unique N-glycosites on 7022 unique N-glycopeptides from 1354 unique glycoproteins were identified. Importantly, we observed an overall increase in glycoprotein, glycopeptide, and glycosite counts in prostate cancer tissue than non-cancerous tissue. We identified biological functions enriched in prostate cancer that relate to cancer development. Additionally, we characterized N-glycosite-specific changes in prostate cancer, demonstrating significant meta- and micro-heterogeneity in N-glycan composition in prostate cancer in comparison to non-cancerous tissue. Our findings support the idea that protein glycosylation is heavily impacted and aberrant in prostate cancer and provide examples of N-glycosite-specific changes that could be exploited for more specific markers of prostate cancer.<\/jats:p>","DOI":"10.1093\/glycob\/cwaf010","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T21:10:51Z","timestamp":1741122651000},"source":"Crossref","is-referenced-by-count":4,"title":["Intact glycopeptide analysis of human prostate tissue reveals site-specific heterogeneity of protein glycosylation in prostate cancer"],"prefix":"10.1093","volume":"35","author":[{"given":"Kathryn L","family":"Kapp","sequence":"first","affiliation":[{"name":"Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine , 3155 Porter Drive, Palo Alto, CA 94304 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Garcia-Marques","sequence":"additional","affiliation":[{"name":"Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine , 3155 Porter Drive, Palo Alto, CA 94304 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M","family":"Totten","sequence":"additional","affiliation":[{"name":"Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine , 3155 Porter Drive, Palo Alto, CA 94304 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Bermudez","sequence":"additional","affiliation":[{"name":"Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine , 3155 Porter Drive, Palo Alto, CA 94304 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheylene","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine , 3155 Porter Drive, Palo Alto, CA 94304 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Urology, Stanford University School of Medicine , Center of Academic Medicine, 453 Quarry Rd, Urology-5656, Palo Alto, California 94304 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3119-873X","authenticated-orcid":false,"given":"Sharon J","family":"Pitteri","sequence":"additional","affiliation":[{"name":"Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine , 3155 Porter Drive, Palo Alto, CA 94304 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"2025031215215833600_ref1","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.bbagen.2011.12.001","article-title":"Glycans as cancer biomarkers","volume":"1820","author":"Adamczyk","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"2025031215215833600_ref2","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-022-00128-4","article-title":"Glycoproteomics","volume":"2","author":"Bagdonaite","year":"2022","journal-title":"Nat Rev Methods Primers"},{"key":"2025031215215833600_ref3","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1002\/cncr.28301","article-title":"Managing localized prostate cancer in the era of prostate-specific antigen screening","volume":"119","author":"Brooks","year":"2013","journal-title":"Cancer"},{"key":"2025031215215833600_ref4","doi-asserted-by":"crossref","first-page":"108181","DOI":"10.1016\/j.celrep.2020.108181","article-title":"Scavenging of labile Heme by Hemopexin is a key checkpoint in cancer growth and metastases","volume":"32","author":"Canesin","year":"2020","journal-title":"Cell Rep"},{"key":"2025031215215833600_ref5","doi-asserted-by":"crossref","first-page":"100010","DOI":"10.1074\/mcp.R120.002093","article-title":"Meta-heterogeneity: evaluating and describing the diversity in glycosylation between sites on the same glycoprotein","volume":"20","author":"Caval","year":"2021","journal-title":"Mol Cell Proteomics"},{"key":"2025031215215833600_ref6","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1002\/pros.22826","article-title":"Increased expression of GCNT1 is associated with altered O-glycosylation of PSA, PAP, and MUC1 in human prostate cancers","volume":"74","author":"Chen","year":"2014","journal-title":"Prostate"},{"key":"2025031215215833600_ref7","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1002\/pros.23034","article-title":"Proteomics analysis of malignant and benign prostate tissue by 2D DIGE\/MS reveals new insights into proteins involved in prostate cancer","volume":"75","author":"Davalieva","year":"2015","journal-title":"Prostate"},{"key":"2025031215215833600_ref8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1373\/clinchem.2009.136333","article-title":"Sweetening the pot: adding glycosylation to the biomarker discovery equation","volume":"56","author":"Drake","year":"2010","journal-title":"Clin Chem"},{"key":"2025031215215833600_ref9","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.3389\/fonc.2019.01482","article-title":"Cancer metastasis: the role of the extracellular matrix and the Heparan Sulfate proteoglycan Perlecan","volume":"9","author":"Elgundi","year":"2019","journal-title":"Front Oncol"},{"key":"2025031215215833600_ref10","doi-asserted-by":"crossref","first-page":"W415","DOI":"10.1093\/nar\/gkae456","article-title":"WebGestalt 2024: faster gene set analysis and new support for metabolomics and multi-omics","volume":"52","author":"Elizarraras","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2025031215215833600_ref11","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1038\/s41598-024-53299-3","article-title":"Identification and characterization of intact glycopeptides in human urine","volume":"14","author":"Garcia-Marques","year":"2024","journal-title":"Sci Rep"},{"key":"2025031215215833600_ref12","doi-asserted-by":"crossref","first-page":"18974","DOI":"10.1038\/s41598-020-75526-3","article-title":"Characterisation of the main PSA glycoforms in aggressive prostate cancer","volume":"10","author":"Gratacos-Mulleras","year":"2020","journal-title":"Sci Rep"},{"key":"2025031215215833600_ref13","first-page":"231","article-title":"Glycosphingolipids as tumor-associated and differentiation markers","volume":"71","author":"Hakomori","year":"1983","journal-title":"J Natl Cancer Inst"},{"key":"2025031215215833600_ref14","first-page":"e54","article-title":"Reply to Greg Shaw, John D. Kelly, and Monique J. Roobol's letter to the editor re: Freddie C. Hamdy, Jenny L. Donovan, J. Athene Lane, et\u00a0al. fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J med 2023;388:1547-58","volume":"85","author":"Hamdy","year":"2024","journal-title":"Eur Urol"},{"key":"2025031215215833600_ref15","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1006\/abbi.1993.1328","article-title":"Isolation, characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins)","volume":"304","author":"Hiraiwa","year":"1993","journal-title":"Arch Biochem Biophys"},{"key":"2025031215215833600_ref16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1476-4598-9-30","article-title":"Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion, migration, and invasion","volume":"9","author":"Hu","year":"2010","journal-title":"Mol Cancer"},{"key":"2025031215215833600_ref17","doi-asserted-by":"crossref","first-page":"136519","DOI":"10.1016\/j.ijbiomac.2024.136519","article-title":"Overexpression of sialyl Lewis(a) carrying mucin-type glycoprotein in prostate cancer cell line contributes to aggressiveness and metastasis","volume":"281","author":"J","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"2025031215215833600_ref18","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00216-016-9880-6","article-title":"Glycans and glycoproteins as specific biomarkers for cancer","volume":"409","author":"Kailemia","year":"2017","journal-title":"Anal Bioanal Chem"},{"key":"2025031215215833600_ref19","doi-asserted-by":"crossref","first-page":"100026","DOI":"10.1074\/mcp.RA120.002320","article-title":"The complexity and dynamics of the tissue Glycoproteome associated with prostate cancer progression","volume":"20","author":"Kawahara","year":"2021","journal-title":"Mol Cell Proteomics"},{"key":"2025031215215833600_ref20","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0014-5793(02)02535-8","article-title":"Abnormal glycosylation and altered Golgi structure in colorectal cancer: dependence on intra-Golgi 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mechanisms and clinical implications","volume":"15","author":"Pinho","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"2025031215215833600_ref31","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R120.002277","article-title":"A pragmatic guide to enrichment strategies for mass spectrometry-based Glycoproteomics","volume":"20","author":"Riley","year":"2021","journal-title":"Mol Cell Proteomics"},{"key":"2025031215215833600_ref32","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.cellimm.2018.03.007","article-title":"Glycosylation in cancer: selected roles in tumour progression, immune modulation and metastasis","volume":"333","author":"Rodrigues","year":"2018","journal-title":"Cell Immunol"},{"key":"2025031215215833600_ref33","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1074\/mcp.R112.026799","article-title":"Developments in the identification of glycan biomarkers for the detection of 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Proteomics"},{"key":"2025031215215833600_ref37","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"2025031215215833600_ref38","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1477-7827-2-2","article-title":"Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer","volume":"2","author":"Stewart","year":"2004","journal-title":"Reprod Biol Endocrinol"},{"key":"2025031215215833600_ref39","doi-asserted-by":"crossref","first-page":"15886","DOI":"10.1038\/s41598-021-95417-5","article-title":"Alterations in protein expression and site-specific N-glycosylation of prostate cancer tissues","volume":"11","author":"Sugar","year":"2021","journal-title":"Sci 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glycans","volume":"27","author":"Varki","year":"2017","journal-title":"Glycobiology"},{"key":"2025031215215833600_ref44","first-page":"77","volume-title":"Essentials of Glycobiology","author":"Varki","year":"2015"},{"key":"2025031215215833600_ref45","doi-asserted-by":"crossref","first-page":"e2200023","DOI":"10.1002\/pmic.202200023","article-title":"Differentially expressed glycoproteins in pre- and post-digital rectal examination urine samples for detecting aggressive prostate cancer","volume":"23","author":"Wang","year":"2023","journal-title":"Proteomics"},{"key":"2025031215215833600_ref46","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1021\/acsmeasuresciau.3c00055","article-title":"In-depth Glycoproteomic assay of urinary prostatic acid phosphatase","volume":"4","author":"Wang","year":"2024","journal-title":"ACS Meas Sci Au"},{"key":"2025031215215833600_ref47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI180282","article-title":"Sialylated glycoproteins suppress 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Chem"}],"container-title":["Glycobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/glycob\/advance-article-pdf\/doi\/10.1093\/glycob\/cwaf010\/62196831\/cwaf010.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/glycob\/article-pdf\/35\/4\/cwaf010\/62196831\/cwaf010.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/glycob\/article-pdf\/35\/4\/cwaf010\/62196831\/cwaf010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T15:22:28Z","timestamp":1741792948000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/glycob\/article\/doi\/10.1093\/glycob\/cwaf010\/8045190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,2,28]]}},"URL":"https:\/\/doi.org\/10.1093\/glycob\/cwaf010","relation":{},"ISSN":["1460-2423"],"issn-type":[{"value":"1460-2423","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2025,2,27]]},"article-number":"cwaf010"}}