{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:51:27Z","timestamp":1791301887749,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R21DK098304"],"award-info":[{"award-number":["1R21DK098304"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U54DK104310"],"award-info":[{"award-number":["U54DK104310"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Expansion of the stromal compartment of the prostate concurrent with fibroblast activation and increased collagenization is now recognized as a pathobiology likely contributing to Lower Urinary Tract Symptoms (LUTS). However, approaches to quantitatively and, ideally, non\u2010invasively, assess prostatic collagenization\n                      <jats:italic>in vivo<\/jats:italic>\n                      are not currently available. This study sought to determine whether human urine could provide a suitable substrate for the identification of pro\u2010fibrotic collagen proteins associated with moderate\/severe LUTS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole urine from two separate age\u2010matched cohorts of men with or without severe LUTS was subjected to Sircol soluble collagen protein, specific gravity, and total protein assays. Samples were assayed fresh or after frozen storage at \u221220\u00b0C or \u221280\u00b0C.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both cohorts demonstrated statistically significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) higher urinary soluble collagen levels in samples from men reporting moderate\/severe LUTS (cases) compared to no\/mild LUTS (controls). Urinary soluble collagen levels did not differ significantly different between the cases of the 2 cohorts or the controls of the 2 cohorts. In both cohorts, urinary specific gravity and whole protein content were modestly higher in cases than controls concurrent with higher collagen content. Responses to medical treatment varied in the LURN cohort, though responses to surgical treatment were overall beneficial. Assays performed using samples stored short\u2010 or long\u2010term at \u221280\u00b0C were highly reproducible.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Urinary soluble collagen levels increase concurrently with moderate\/severe LUTS, and are stable in urine after long\u2010term storage at \u221280\u00b0C. These findings suggest that urinary soluble collagen levels may serve as suitable diagnostic biomarkers for prostatic collagenization consistent with fibrosis in association with LUTS. Potentially, urinary soluble collagen levels may be used as surrogate endpoint biomarkers to assess the efficacy of anti\u2010fibrotic medical or surgical therapies to decrease prostatic urethral obstruction or resistance, and alleviate LUTS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70258","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:51:50Z","timestamp":1791298310000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary Soluble Collagen Levels Are Associated With Moderate\/Severe LUTS"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2348-9590","authenticated-orcid":false,"given":"Marissa","family":"Sarna\u2010McCarthy","sequence":"first","affiliation":[{"name":"The Center for Personalized Cancer Therapy, The University of Massachusetts Boston Boston Massachusetts USA"},{"name":"Departmentsof Biology The University of Massachusetts Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2307-0708","authenticated-orcid":false,"given":"Claweens","family":"Quetant","sequence":"additional","affiliation":[{"name":"The Center for Personalized Cancer Therapy, The University of Massachusetts Boston Boston Massachusetts USA"},{"name":"Departmentsof Biology The University of Massachusetts Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0914-9826","authenticated-orcid":false,"given":"Quentin","family":"D'Arcy","sequence":"additional","affiliation":[{"name":"The Center for Personalized Cancer Therapy, The University of Massachusetts Boston Boston Massachusetts USA"},{"name":"Departmentsof Biology The University of Massachusetts Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8837-3616","authenticated-orcid":false,"given":"Richard","family":"Caesar","sequence":"additional","affiliation":[{"name":"The Center for Personalized Cancer Therapy, The University of Massachusetts Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5108-8108","authenticated-orcid":false,"given":"Kourosh","family":"Zarringhalam","sequence":"additional","affiliation":[{"name":"The Center for Personalized Cancer Therapy, The University of Massachusetts Boston Boston Massachusetts USA"},{"name":"Department of Mathematics The University of Massachusetts Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-2221","authenticated-orcid":false,"given":"Jill A.","family":"Macoska","sequence":"additional","affiliation":[{"name":"The Center for Personalized Cancer Therapy, The University of Massachusetts Boston Boston Massachusetts USA"},{"name":"Departmentsof Biology The University of Massachusetts Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"11","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"e754","DOI":"10.1016\/S2666-7568(22)00213-6","article-title":"The Global, Regional, and National Burden of Benign Prostatic Hyperplasia in 204 Countries and Territories From 2000 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"3","author":"Awedew A. F.","year":"2022","journal-title":"Lancet Healthy Longevity"},{"issue":"3","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ucl.2016.04.001","article-title":"The Epidemiology of Benign Prostatic Hyperplasia Associated With Lower Urinary Tract Symptoms","volume":"43","author":"Egan K. B.","year":"2016","journal-title":"Urologic Clinics of North America"},{"issue":"1","key":"e_1_2_11_4_1","first-page":"19","article-title":"Medical Management of Lower Urinary Tract Symptoms","volume":"11","author":"Laborde E. E.","year":"2009","journal-title":"Reviews in Urology"},{"issue":"3","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0149-2918(07)80077-4","article-title":"A Review of Combination Therapy in Patients With Benign Prostatic Hyperplasia","volume":"29","author":"McVary K. T.","year":"2007","journal-title":"Clinical Therapeutics"},{"issue":"12","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","DOI":"10.1007\/s11934-020-01009-7","article-title":"Tadalafil Alone or in Combination With Tamsulosin for the Management for LUTS\/BPH and ED","volume":"21","author":"Sebastianelli A.","year":"2020","journal-title":"Current Urology Reports"},{"issue":"1","key":"e_1_2_11_7_1","first-page":"10","article-title":"BPH Update: Medical Versus Interventional Management","volume":"23","author":"Blankstein U.","year":"2016","journal-title":"Canadian Journal of Urology"},{"issue":"9","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/nrurol.2013.149","article-title":"Prostatic Fibrosis, Lower Urinary Tract Symptoms, and BPH","volume":"10","author":"Rodriguez\u2010Nieves J. A.","year":"2013","journal-title":"Nature Reviews Urology"},{"issue":"6","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1097\/JU.0000000000000385","article-title":"Prostate Transition Zone Fibrosis Is Associated With Clinical Progression in the MTOPS Study","volume":"202","author":"Macoska J. A.","year":"2019","journal-title":"Journal of Urology"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/978-3-032-05273-5_11","article-title":"Collagen in Fibrotic Diseases","volume":"113","author":"Fertala A.","year":"2026","journal-title":"Sub\u2013Cellular Biochemistry"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-3-032-05273-5_10","article-title":"Collagen Mechanics","volume":"113","author":"Szarek P.","year":"2026","journal-title":"Sub\u2013Cellular Biochemistry"},{"issue":"4","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.juro.2017.10.035","article-title":"Baseline Lower Urinary Tract Symptoms in Patients Enrolled in LURN: A Prospective, Observational Cohort Study","volume":"199","author":"Cameron A. P.","year":"2018","journal-title":"Journal of Urology"},{"issue":"11","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","DOI":"10.1007\/s11934-021-01070-w","article-title":"Lower Urinary Tract Stenosis Following Surgery for Benign Prostatic Hyperplasia","volume":"22","author":"Kurtzman J. T.","year":"2021","journal-title":"Current Urology Reports"},{"issue":"2","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.4103\/aja.aja_126_19","article-title":"Transurethral Resection of the Prostate Stricture Management","volume":"22","author":"Wang J. W.","year":"2020","journal-title":"Asian Journal of Andrology"},{"issue":"4","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.4103\/UA.UA_165_19","article-title":"Post\u2010Transurethral Resection of Prostate Urethral Strictures: Are They Often Underreported? A Single\u2010Center Retrospective Observational Cohort Study","volume":"13","author":"Sekar H.","year":"2021","journal-title":"Urology Annals"},{"issue":"12","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/s41416-019-0472-z","article-title":"CE\u2010MS\u2010Based Urinary Biomarkers to Distinguish Non\u2010Significant From Significant Prostate Cancer","volume":"120","author":"Frantzi M.","year":"2019","journal-title":"British Journal of Cancer"},{"issue":"4","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers15041166","article-title":"Mass Spectrometry\u2010Based Biomarkers to Detect Prostate Cancer: A Multicentric Study Based on Non\u2010Invasive Urine Collection Without Prior Digital Rectal Examination","volume":"15","author":"Frantzi M.","year":"2023","journal-title":"Cancers"},{"issue":"3","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms27031585","article-title":"Prostate Cancer\u2010Associated Fibroblasts: A Review on CAF Functions, Heterogeneity, Resistance Mechanisms, and Future in a Chip","volume":"27","author":"Lupsa N.","year":"2026","journal-title":"International Journal of Molecular Sciences"},{"issue":"2","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/pros.23929","article-title":"Heterogeneity of Human Prostate Carcinoma\u2010Associated Fibroblasts Implicates a Role for Subpopulations in Myeloid Cell Recruitment","volume":"80","author":"Vickman R. E.","year":"2020","journal-title":"Prostate"},{"issue":"1","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.bbcan.2014.04.001","article-title":"Prostate\u2010Specific Antigen and Other Serum and Urine Markers in Prostate Cancer","volume":"1846","author":"Stephan C.","year":"2014","journal-title":"Biochimica et Biophysica Acta (BBA) \u2010 Reviews on Cancer"},{"key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.urology.2019.03.014","article-title":"A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways That Associate With Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study","volume":"129","author":"Helfand B. T.","year":"2019","journal-title":"Urology"},{"issue":"7","key":"e_1_2_11_22_1","first-page":"809","article-title":"Circulating Proteomic Signatures of Chronological Age","volume":"70","author":"Menni C.","year":"2015","journal-title":"Journals of Gerontology: Series A"},{"issue":"1","key":"e_1_2_11_23_1","first-page":"1","article-title":"Renal Aging and Fibrosis in the Elderly: Frontiers in Non\u2010Invasive Assessment","volume":"4","author":"Zhang Q. Ca. J.","year":"2026","journal-title":"Fibrosis"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70258","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pros.70258","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70258","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:51:55Z","timestamp":1791298315000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.70258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":22,"alternative-id":["10.1002\/pros.70258"],"URL":"https:\/\/doi.org\/10.1002\/pros.70258","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"assertion":[{"value":"2026-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"pros.70258"}}