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BPH can lead to bothersome lower urinary tract symptoms (LUTS), which may reduce quality of life. Many patients fail current treatment options and may progress to surgical intervention. Furthermore, diagnosis is reliant on symptom questionnaires and the cause of LUTS can be difficult to distinguish. Currently, BPH can only be definitively diagnosed through histological analysis of prostate tissue, which is not the standard of care. The resulting lack of clinical tissue samples is a major limitation in investigating disease pathology. Improved understanding of disease development and progression, along with objective biomarkers of disease, is needed for BPH. This investigation uses mass spectrometry (MS)-based proteomics and glycoproteomics to compare healthy prostate tissue with prostate tissue affected by BPH to address this gap in knowledge. By integrating proteomics and glycoproteomics, we identified 206 proteins and 44 glycopeptides that were significantly altered between BPH and control samples. These findings provide deeper insight into disease-associated pathways and may facilitate the identification of clinically relevant targets for further investigation.<\/jats:p>","DOI":"10.1021\/jasms.6c00143","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:01:58Z","timestamp":1785884518000},"page":"2103-2111","source":"Crossref","is-referenced-by-count":0,"title":["High-Throughput Proteomic\nand Glycoproteomic Analyses\nin Benign Prostatic Hyperplasia"],"prefix":"10.1021","volume":"37","author":[{"given":"Feixuan","family":"Wu","sequence":"first","affiliation":[{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis E.","family":"Adrian","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8032-857X","authenticated-orcid":true,"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Kai","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Lu","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas W.","family":"Strand","sequence":"additional","affiliation":[{"name":"UT Southwestern Medical Center , , , ,","place":["Dallas, Texas, United States, 75390"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Ricke","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0056-3869","authenticated-orcid":true,"given":"Lingjun","family":"Li","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]},{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53706"]},{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53706"]},{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]},{"name":"University of Wisconsin-Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"3","key":"2026090311505790700_cit1","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/S0022-5347(17)49698-4","article-title":"The development\nof human benign prostatic hyperplasia with age","volume":"132","author":"Berry","year":"1984","journal-title":"J. Urol."},{"issue":"3","key":"2026090311505790700_cit2","first-page":"332","article-title":"[Lower urinary tract\nsymptoms and male sexual dysfunction:\nthe multinational survey of the aging.male (MSAM-7)]","volume":"14","author":"Rosen","year":"2004","journal-title":"Prog. Urol."},{"key":"2026090311505790700_cit3","article-title":"Benign Prostatic\nHyperplasia","volume-title":"StatPearls","author":"Ng","year":"2025"},{"issue":"3","key":"2026090311505790700_cit4","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3949\/ccjm.91a.23027","article-title":"Medical management\nof benign prostatic\nhyperplasia","volume":"91","author":"Haile","year":"2024","journal-title":"Clevel Clin. J. Med."},{"key":"2026090311505790700_cit5","doi-asserted-by":"publisher","first-page":"16031","DOI":"10.1038\/nrdp.2016.31","article-title":"Benign prostatic\nhyperplasia","volume":"2","author":"Chughtai","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"issue":"4","key":"2026090311505790700_cit6","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.juro.2012.06.007","article-title":"Prostatic fibrosis\nis associated with lower urinary tract symptoms","volume":"188","author":"Ma","year":"2012","journal-title":"J. Urol."},{"issue":"6","key":"2026090311505790700_cit7","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1097\/JU.0000000000000385","article-title":"Prostate\nTransition Zone Fibrosis is Associated with Clinical Progression in\nthe MTOPS Study","volume":"202","author":"Macoska","year":"2019","journal-title":"J. Urol."},{"key":"2026090311505790700_cit8","doi-asserted-by":"publisher","first-page":"1494476","DOI":"10.3389\/fimmu.2024.1494476","article-title":"Infiltrating\nlipid-rich macrophage subpopulations identified as a regulator of\nincreasing prostate size in human benign prostatic hyperplasia","volume":"15","author":"Lanman","year":"2025","journal-title":"Front. 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Proteome Res."},{"key":"2026090311505790700_cit15","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3791\/63735","article-title":"A Spin-Tip Enrichment Strategy for\nSimultaneous Analysis of N-Glycopeptides and Phosphopeptides from\nHuman Pancreatic Tissues","author":"Tabang","year":"2022","journal-title":"J. Vis. Exp."},{"issue":"3","key":"2026090311505790700_cit16","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1021\/ac503276z","article-title":"High-resolution\nenabled 12-plex DiLeu\nisobaric tags for quantitative proteomics","volume":"87","author":"Frost","year":"2015","journal-title":"Anal.\nChem."},{"issue":"7","key":"2026090311505790700_cit17","doi-asserted-by":"publisher","first-page":"100969","DOI":"10.1016\/j.mcpro.2025.100969","article-title":"Proteome-Wide\nInvestigation of Proline Hydroxylation in Pancreatic Ductal Adenocarcinoma\nUsing DiLeu Isobaric Labeling Strategy","volume":"24","author":"Wu","year":"2025","journal-title":"Mol.\nCell. Proteomics"},{"key":"2026090311505790700_cit18","doi-asserted-by":"publisher","first-page":"345231","DOI":"10.1016\/j.aca.2026.345231","article-title":"High-throughput simultaneous\nquantification of glycopeptides and phosphopeptides enabled by 12-plex\nDiLeu isobaric tags and dual-functional Titanium(IV)-IMAC material","volume":"1395","author":"Wu","year":"2026","journal-title":"Anal. Chim. Acta"},{"issue":"9","key":"2026090311505790700_cit19","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational\nplatform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. 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Dis."},{"issue":"5","key":"2026090311505790700_cit22","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/pros.24661","article-title":"Transcriptomic analysis of benign prostatic\nhyperplasia identifies critical pathways in prostatic overgrowth and\n5-alpha reductase inhibitor resistance","volume":"84","author":"Jin","year":"2024","journal-title":"Prostate"},{"issue":"1","key":"2026090311505790700_cit23","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1038\/s41467-022-29719-1","article-title":"TNF is a potential therapeutic target to suppress\nprostatic inflammation and hyperplasia in autoimmune disease","volume":"13","author":"Vickman","year":"2022","journal-title":"Nat. Commun."},{"issue":"1","key":"2026090311505790700_cit24","first-page":"53","article-title":"Claudin-1 down-regulation in the prostate is associated with aging\nand increased infiltration of inflammatory cells in BPH","volume":"9","author":"Pascal","year":"2021","journal-title":"Am. J. Clin. Exp. Urol."},{"issue":"1","key":"2026090311505790700_cit25","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1002\/pros.23100","article-title":"Oxidative stress promotes benign\nprostatic hyperplasia","volume":"76","author":"Vital","year":"2016","journal-title":"Prostate"},{"issue":"4","key":"2026090311505790700_cit26","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1021\/acs.jproteome.9b00451","article-title":"Spatiotemporal Proteomics\nReveals the Molecular Consequences of Hormone Treatment in a Mouse\nModel of Lower Urinary Tract Dysfunction","volume":"19","author":"Thomas","year":"2020","journal-title":"J.\nProteome Res."},{"key":"2026090311505790700_cit27","doi-asserted-by":"publisher","DOI":"10.1101\/2025.06.26.661634","article-title":"HILIC-Enabled Mass Spectrometric Discovery\nof Novel\nEndogenous and Glycosylated Neuropeptides in the American Lobster\nNervous System","author":"Tran","year":"2025","journal-title":"BioRxiv"},{"issue":"48","key":"2026090311505790700_cit28","doi-asserted-by":"publisher","first-page":"17637","DOI":"10.1021\/acs.analchem.3c03342","article-title":"6-Plex mdSUGAR Isobaric-Labeling Guide Fingerprint\nEmbedding for\nGlycomics Analysis","volume":"95","author":"Ma","year":"2023","journal-title":"Anal. Chem."},{"issue":"10","key":"2026090311505790700_cit29","doi-asserted-by":"publisher","first-page":"102129","DOI":"10.1016\/j.labinv.2024.102129","article-title":"Establishing and Characterizing the Molecular\nProfiles, Cellular Features, and Clinical Utility of a Patient-Derived\nXenograft Model Using Benign Prostatic Tissues","volume":"104","author":"Polasko","year":"2024","journal-title":"Lab. Invest."},{"issue":"1","key":"2026090311505790700_cit30","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s12014-023-09439-4","article-title":"Development\nof a predictive model to distinguish prostate\ncancer from benign prostatic hyperplasia by integrating serum glycoproteomics\nand clinical variables","volume":"20","author":"Gabriele","year":"2023","journal-title":"Clin. Proteomics"},{"issue":"10","key":"2026090311505790700_cit31","doi-asserted-by":"publisher","first-page":"103168","DOI":"10.1016\/j.isci.2021.103168","article-title":"Site-specific N-glycosylation\nof integrin alpha2 mediates collagen-dependent\ncell survival","volume":"24","author":"Huang","year":"2021","journal-title":"iScience"},{"key":"2026090311505790700_cit32","doi-asserted-by":"publisher","first-page":"751637","DOI":"10.3389\/fmolb.2021.751637","article-title":"An Overview of Glycosylation\nand\nits Impact on Cardiovascular Health and Disease","volume":"8","author":"Loaeza-Reyes","year":"2021","journal-title":"Front. Mol. Biosci."},{"issue":"5","key":"2026090311505790700_cit33","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1007\/s00125-024-06109-4","article-title":"Elevated\nITGA1 levels in type 2 diabetes: implications for cardiac function\nimpairment","volume":"67","author":"Su","year":"2024","journal-title":"Diabetologia"},{"issue":"2","key":"2026090311505790700_cit34","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/path.5751","article-title":"Single-cell\nanalysis of mouse and human prostate\nreveals novel fibroblasts with specialized distribution and microenvironment\ninteractions","volume":"255","author":"Joseph","year":"2021","journal-title":"J. Pathol."},{"issue":"1","key":"2026090311505790700_cit35","doi-asserted-by":"publisher","first-page":"21029","DOI":"10.1038\/s41598-024-71137-4","article-title":"Characterization\nof prostate macrophage\nheterogeneity, foam cell markers, and CXCL17 upregulation in a mouse\nmodel of steroid hormone imbalance","volume":"14","author":"Silver","year":"2024","journal-title":"Sci. Rep."},{"issue":"1","key":"2026090311505790700_cit36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/proteomes6010001","article-title":"Comparative Proteomics Analysis of\nUrine Reveals Down-Regulation\nof Acute Phase Response Signaling and LXR\/RXR Activation Pathways\nin Prostate Cancer","volume":"6","author":"Davalieva","year":"2018","journal-title":"Proteomes"},{"issue":"1","key":"2026090311505790700_cit37","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/s41419-025-08027-8","article-title":"ZC3H4, a novel regulator of mitochondrial\ncomplex I, impacts prostate stromal cell senescence, attachment, adhesion\nand anoikis resistance","volume":"16","author":"Liu","year":"2025","journal-title":"Cell Death Dis."},{"issue":"2","key":"2026090311505790700_cit38","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.cccn.2005.03.026","article-title":"Expression analysis\nand prognostic significance of human kallikrein 11 in prostate cancer","volume":"357","author":"Stavropoulou","year":"2005","journal-title":"Clin. Chim. Acta"},{"issue":"12","key":"2026090311505790700_cit39","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1093\/glycob\/cwv058","article-title":"Analysis of site-specific\nN-glycan remodeling in the endoplasmic reticulum and the Golgi","volume":"25","author":"Hang","year":"2015","journal-title":"Glycobiology"},{"issue":"1","key":"2026090311505790700_cit40","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/s41420-024-02180-3","article-title":"Biological function\nof sialic acid and sialylation in human health and disease","volume":"10","author":"Zhu","year":"2024","journal-title":"Cell Death Discovery"},{"issue":"5","key":"2026090311505790700_cit41","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.chembiol.2018.02.005","article-title":"Unmasking Fucosylation:\nfrom Cell Adhesion to Immune System Regulation and Diseases","volume":"25","author":"Li","year":"2018","journal-title":"Cell Chem. Biol."},{"issue":"8","key":"2026090311505790700_cit42","doi-asserted-by":"publisher","first-page":"13689","DOI":"10.3390\/molecules200813689","article-title":"Glycoprotein Quality Control and\nEndoplasmic Reticulum Stress","volume":"20","author":"Wang","year":"2015","journal-title":"Molecules"},{"issue":"6","key":"2026090311505790700_cit43","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1021\/acs.jproteome.9b00003","article-title":"Deciphering the Roles of N-Glycans on Collagen-Platelet\nInteractions","volume":"18","author":"Toonstra","year":"2019","journal-title":"J. Proteome Res."},{"issue":"12","key":"2026090311505790700_cit44","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nrm3902","article-title":"Extracellular matrix assembly: a multiscale deconstruction","volume":"15","author":"Mouw","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"1","key":"2026090311505790700_cit45","doi-asserted-by":"publisher","first-page":"6509","DOI":"10.1038\/s41598-018-24270-w","article-title":"Multi-lectin Affinity Chromatography\nand Quantitative Proteomic Analysis Reveal Differential Glycoform\nLevels between Prostate Cancer and Benign Prostatic Hyperplasia Sera","volume":"8","author":"Totten","year":"2018","journal-title":"Sci. Rep."},{"issue":"5","key":"2026090311505790700_cit46","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202304274","article-title":"YAP1 Recognizes\nInflammatory and Mechanical Cues to Exacerbate Benign Prostatic Hyperplasia\nvia Promoting Cell Survival and Fibrosis","volume":"11","author":"Lin","year":"2024","journal-title":"Adv.\nSci."}],"container-title":["Journal of the American\nSociety for Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jasms.6c00143","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/9\/2103\/66394484\/jasms.6c00143.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/9\/2103\/66394484\/jasms.6c00143.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:24:56Z","timestamp":1788452696000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jamsef\/article\/37\/9\/2103\/5243703\/High-Throughput-Proteomic-and-Glycoproteomic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":46,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,8,4]]},"published-print":{"date-parts":[[2026,9,2]]}},"URL":"https:\/\/doi.org\/10.1021\/jasms.6c00143","relation":{},"ISSN":["1044-0305","1879-1123"],"issn-type":[{"value":"1044-0305","type":"print"},{"value":"1879-1123","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]}}}