{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:40:37Z","timestamp":1792428037079,"version":"4.5.0"},"reference-count":25,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Buddhist Tzu Chi Medical Foundation","award":["TCMMP105-02-03"],"award-info":[{"award-number":["TCMMP105-02-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study applied K-means cluster analysis to urinary biomarker profiles in interstitial cystitis\/bladder pain syndrome (IC\/BPS) patients, aiming to provide a new perspective on disease classification and its clinical relevance. We retrospectively analyzed urine samples from 127 IC\/BPS patients and 30 controls. The urinary levels of 10 inflammatory cytokines and three oxidative stress markers (8-hydroxy-2-deoxyguanosin [8-OHdG], 8-isoprostane, and total antioxidant capacity [TAC]) were quantified. K-means clustering was performed to identify biomarker-based patient subgroups. IC\/BPS patients exhibited significantly elevated urinary levels of Eotaxin, MCP-1, NGF, 8-OHdG, 8-isoprostane, and TAC compared to controls (all p &lt; 0.05). K-means clustering identified four distinct subgroups. Cluster 4, characterized by the highest levels of inflammatory and oxidative stress biomarkers, comprised 85% ESSIC type 2 IC\/BPS patients and exhibited the lowest visual analogue scale (VAS) pain scores and maximal bladder capacity (MBC). Correlation analysis revealed distinct cluster-specific associations between biomarker levels and clinical parameters, including the VAS pain score, MBC, the grade of glomerulation, and treatment outcomes. Applying K-means clustering to urinary inflammatory and oxidative stress biomarkers provides a new perspective on disease classification, identifying IC\/BPS subtypes with distinct clinical and biochemical characteristics. This approach may refine disease phenotyping and guide personalized treatment strategies in the future.<\/jats:p>","DOI":"10.3390\/ijms26083712","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T03:59:06Z","timestamp":1744689546000},"page":"3712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Applying K-Means Cluster Analysis to Urinary Biomarkers in Interstitial Cystitis\/Bladder Pain Syndrome: A New Perspective on Disease Classification"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-1574","authenticated-orcid":false,"given":"Yuan-Hong","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"},{"name":"Department of Urology, School of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Fong","family":"Jhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"},{"name":"Department of Urology, School of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4946-8064","authenticated-orcid":false,"given":"Jen-Hung","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7165-4771","authenticated-orcid":false,"given":"Hann-Chorng","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"},{"name":"Department of Urology, School of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1007\/s00192-019-03970-5","article-title":"Variations in bladder pain syndrome\/interstitial cystitis (IC) definitions, pathogenesis, diagnostics and treatment: A systematic review and evaluation of national and international guidelines","volume":"30","author":"Pape","year":"2019","journal-title":"Int. Urogynecol. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/iju.12308","article-title":"Bladder afferent hyperexcitability in bladder pain syndrome\/interstitial cystitis","volume":"21","author":"Yoshimura","year":"2014","journal-title":"Int. J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.eururo.2012.05.023","article-title":"Mapping of pain phenotypes in female patients with bladder pain syndrome\/interstitial cystitis and controls","volume":"62","author":"Tripp","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11884-020-00599-9","article-title":"Phenotypes of BPS\/IC","volume":"15","author":"Malde","year":"2020","journal-title":"Curr. Bladder Dysfunct. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1097\/JU.0000000000000257","article-title":"Biomarkers Implicated in Lower Urinary Tract Symptoms: Systematic Review and Pathway Analyses","volume":"202","author":"Siddiqui","year":"2019","journal-title":"J. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41585-023-00850-y","article-title":"Mechanisms of oxidative stress in interstitial cystitis\/bladder pain syndrome","volume":"21","author":"Mohammad","year":"2024","journal-title":"Nat. Rev. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"F1391","DOI":"10.1152\/ajprenal.00051.2020","article-title":"Urine cytokines as biomarkers for diagnosing interstitial cystitis\/bladder pain syndrome and mapping its clinical characteristics","volume":"318","author":"Jiang","year":"2020","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jiang, Y.H., Jhang, J.F., Ho, H.C., Chiou, D.Y., and Kuo, H.C. (2022). Urine Oxidative Stress Biomarkers as Novel Biomarkers in Interstitial Cystitis\/Bladder Pain Syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071701"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00345-024-04843-3","article-title":"Combination of urinary biomarkers and machine-learning models provided a higher predictive accuracy to predict long-term treatment outcomes of patients with interstitial cystitis\/bladder pain syndrome","volume":"42","author":"Jhang","year":"2024","journal-title":"World J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"42740","DOI":"10.1109\/ACCESS.2018.2852648","article-title":"Revisiting K-Means and Topic Modeling, a Comparison Study to Cluster Arabic Documents","volume":"6","author":"Alhawarat","year":"2018","journal-title":"IEEE Access"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"80716","DOI":"10.1109\/ACCESS.2020.2988796","article-title":"Unsupervised K-Means Clustering Algorithm","volume":"8","author":"Sinaga","year":"2020","journal-title":"IEEE Access"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.eururo.2007.09.019","article-title":"Diagnostic criteria, classification, and nomenclature for painful bladder syndrome\/interstitial cystitis: An ESSIC proposal","volume":"53","author":"Nordling","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.juro.2009.02.122","article-title":"Clinical phenotyping of women with interstitial cystitis\/painful bladder syndrome: A key to classification and potentially improved management","volume":"182","author":"Nickel","year":"2009","journal-title":"J. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/JU.0000000000002756","article-title":"Diagnosis and Treatment of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"208","author":"Clemens","year":"2022","journal-title":"J. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lin, H.Y., Lu, J.H., Chuang, S.M., Chueh, K.S., Juan, T.J., Liu, Y.C., and Juan, Y.S. (2021). Urinary Biomarkers in Interstitial Cystitis\/Bladder Pain Syndrome and Its Impact on Therapeutic Outcome. Diagnostics, 12.","DOI":"10.3390\/diagnostics12010075"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yu, W.R., Jiang, Y.H., Jhang, J.F., and Kuo, H.C. (2022). Use of Urinary Cytokine and Chemokine Levels for Identifying Bladder Conditions and Predicting Treatment Outcomes in Patients with Interstitial Cystitis\/Bladder Pain Syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051149"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrurol.2012.178","article-title":"Neurotrophins as regulators of urinary bladder function","volume":"9","author":"Ochodnicky","year":"2012","journal-title":"Nat. Rev. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1007\/s00192-019-04075-9","article-title":"Biomarkers in the diagnosis and symptom assessment of patients with bladder pain syndrome: A systematic review","volume":"30","author":"Magalhaes","year":"2019","journal-title":"Int. Urogynecol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1097\/JU.0000000000000250","article-title":"Clustering of Patients with Interstitial Cystitis\/Bladder Pain Syndrome and Chronic Prostatitis\/Chronic Pelvic Pain Syndrome","volume":"202","author":"Lai","year":"2019","journal-title":"J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.urology.2024.03.043","article-title":"Risk Classification for Interstitial Cystitis\/Bladder Pain Syndrome Using Machine Learning Based Predictions","volume":"189","author":"Lamb","year":"2024","journal-title":"Urology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Janicki, J.J., Zwaans, B.M.M., Bartolone, S.N., Ward, E.P., and Chancellor, M.B. (2024). Advancing Interstitial Cystitis\/Bladder Pain Syndrome (IC\/BPS) Diagnosis: A Comparative Analysis of Machine Learning Methodologies. Diagnostics, 14.","DOI":"10.3390\/diagnostics14232734"},{"key":"ref_22","first-page":"624","article-title":"Role of cystoscopy and hydrodistention in the diagnosis of interstitial cystitis\/bladder pain syndrome","volume":"4","author":"Ens","year":"2015","journal-title":"Transl. Androl. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1177\/1756287217731009","article-title":"Treatment of ulcerative compared to non-ulcerative interstitial cystitis with hyperbaric oxygen: A pilot study","volume":"9","author":"Wenzler","year":"2017","journal-title":"Ther. Adv. Urol."},{"key":"ref_24","first-page":"197","article-title":"Intravesical onabotulinumtoxinA injections for refractory painful bladder syndrome","volume":"15","author":"Chung","year":"2012","journal-title":"Pain. Physician"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v061.i06","article-title":"NbClust: An R Package for Determining the Relevant Number of Clusters in a Data Set","volume":"61","author":"Charrad","year":"2014","journal-title":"J. Stat. Softw."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3712\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:14:30Z","timestamp":1760030070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":25,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083712"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083712","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]}}}