{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:02:58Z","timestamp":1768867378602,"version":"3.49.0"},"reference-count":22,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"Vedeck\u00e1 Grantov\u00e1 Agent\u00fara M\u0160VVa\u0160 SR a SAV","doi-asserted-by":"publisher","award":["01\/0136\/18"],"award-info":[{"award-number":["01\/0136\/18"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Bladder cancer (BC) is the most common type of carcinoma of the urological system. Recently, there has been an increasing interest in non-invasive diagnostic tumor markers due to the invasive attribute of cystoscopy, which is still considered the gold standard diagnostic method. However, markers published in the literature so far do not meet expectations for replacing cystoscopy due to their low specificity and excessively high false-positive results, which can be mainly caused by frequently occurring hematuria also in benign cases. No reliable non-invasive method has yet been identified that can distinguish patients with bladder cancer and non-malignant hematuria patients. Our work examined the possibilities of non-targeted biomarkers of urine to distinguish patients with malignant and non-malignant diseases of the bladder using 3D HPLC in combination with computer processing of multiple datasets. Urine samples from 47 patients, 23 patients with bladder cancer (BC) and 24 patients with non-malignant hematuria (NMHU), were enrolled in clinical trials. For the separation and subsequent analysis of a large number of urine components, 3D HPLC (high-performance liquid chromatography) with an absorption and fluorescence detector was used. The obtained dataset was further subjected to various uni- and multi-dimensional statistical analyses and mathematical modeling. We found 334 chromatographic peaks, of which 18 peaks were identified as significantly different for BC and NMHU patients. Using receiver operating characteristic (ROC) analysis, we assessed the informative ability of significant chromatographic peaks (90% sensitivity and 74% specificity). By logistic regression, we identified the optimal and simplified set of seven chromatographic peaks (5 absorptions plus 2 fluorescence) with strong classification power (100% sensitivity and 100% specificity) for distinguishing patients with bladder cancer and those with non-malignant hematuria. Partial least square discriminant analysis (PLS-DA) model and orthogonal projection to latent structure discriminant analysis (OPLS-DA) with 100% sensitivity and 96% specificity were used to distinguish BC and NMHU patients. Multivariate statistical analysis of urinary metabolomic profiles of patients revealed that BC patients can be discriminated from NMHU patients and the results can likely contribute to an early and non-invasive diagnosis of BC.<\/jats:p>","DOI":"10.3390\/diagnostics11101793","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T12:29:14Z","timestamp":1632832154000},"page":"1793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Multiple Chromatographic Analysis of Urine in the Detection of Bladder Cancer"],"prefix":"10.3390","volume":"11","author":[{"given":"Daniela","family":"D\u017eubinsk\u00e1","sequence":"first","affiliation":[{"name":"Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University in Bratislava, Mlynsk\u00e1 Dolina, 842 48 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milan","family":"Zvar\u00edk","sequence":"additional","affiliation":[{"name":"Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University in Bratislava, Mlynsk\u00e1 Dolina, 842 48 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris","family":"Koll\u00e1rik","sequence":"additional","affiliation":[{"name":"Department of Urology, University Hospital of Bratislava, Antolsk\u00e1 11, 851 07 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libu\u0161a","family":"\u0160ikurov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University in Bratislava, Mlynsk\u00e1 Dolina, 842 48 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"ref_1","unstructured":"(2019, March 24). International Agency for Research on Cancer. Available online: http:\/\/gco.iarc.fr\/."},{"key":"ref_2","first-page":"23","article-title":"Bladder Cancer Academy 2019 Selected Summaries","volume":"21","author":"Schulster","year":"2019","journal-title":"Rev. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.chroma.2013.10.002","article-title":"Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach","volume":"1318","author":"Alberice","year":"2013","journal-title":"J. Chromatogr. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/j.1464-410X.2011.10664.x","article-title":"Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: Results for 778 patients from a hospital haematuria clinic","volume":"110","author":"Blick","year":"2012","journal-title":"BJU Int."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Batista, R., Vinagre, N., Meireles, S., Vinagre, J., Prazeres, H., Le\u00e3o, R., M\u00e1ximo, V., and Soares, P. (2020). Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review. Diagnostics, 10.","DOI":"10.3390\/diagnostics10010039"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Oliveira, M.C., Caires, H.R., Oliveira, M.J., Fraga, A., Vasconcelos, M.H., and Ribeiro, R. (2020). Urinary Biomarkers in Bladder Cancer: Where Do We Stand and Potential Role of Extracellular Vesicles. Cancers, 12.","DOI":"10.3390\/cancers12061400"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9172","DOI":"10.1038\/s41598-018-27538-3","article-title":"Bladder cancer recurrence surveillance by urine metabolomics analysis","volume":"8","author":"Loras","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"38802","DOI":"10.18632\/oncotarget.16393","article-title":"Metabolite marker discovery for the detection of bladder cancer by comparative metabolomics","volume":"8","author":"Shao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wang, Z., Liu, X., Liu, X., Sun, H., Guo, Z., Zheng, G., Zhang, Y., and Sun, W. (2019). UPLC-MS based urine untargeted metabolomic analyses to differentiate bladder cancer from renal cell carcinoma. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6354-1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14789450.2019.1583105","article-title":"Recent advances in the metabolomic study of bladder cancer","volume":"16","author":"Amara","year":"2019","journal-title":"Expert Rev. Proteom."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1046\/j.1523-5394.2002.106011.x","article-title":"Bladder cancer: Epidemiology, diagnosis, and management","volume":"10","author":"Pashos","year":"2002","journal-title":"Cancer Pract."},{"key":"ref_12","first-page":"223","article-title":"Quality-control analytical methods: High-performance liquid chromatography","volume":"8","author":"Kupiec","year":"2004","journal-title":"Int. J. Pharm. Compd."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"533","DOI":"10.4149\/neo_2013_069","article-title":"Fluorescence characteristics of human urine from normal individuals and ovarian cancer patients","volume":"60","author":"Zvarik","year":"2013","journal-title":"Neoplasma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4149\/neo_2018_170610N420","article-title":"Urinary fluorescence analysis in diagnosis of bladder cancer","volume":"65","author":"Kollarik","year":"2017","journal-title":"Neoplasma"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1007\/s00345-018-2505-2","article-title":"Can urinary biomarkers replace cystoscopy?","volume":"37","author":"Maas","year":"2019","journal-title":"World J. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/S0022-5347(05)65290-1","article-title":"The BTA stat test is nonspecific for hematuria: An experimental hematuria model","volume":"167","author":"Oge","year":"2002","journal-title":"J. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.urology.2008.04.051","article-title":"Nuclear matrix protein 22 as adjunct to urine cytology and cystoscopy in follow-up of superficial TCC of urinary bladder","volume":"73","author":"Gupta","year":"2009","journal-title":"Urology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s00345-012-0935-9","article-title":"Urinary BTA: Indicator of bladder cancer or of hematuria","volume":"30","author":"Miyake","year":"2012","journal-title":"World J. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.4111\/kju.2010.51.2.88","article-title":"Usefulness of the NMP22BladderChek Test for Screening and Follow-up of Bladder Cancer","volume":"51","author":"Choi","year":"2010","journal-title":"Korean J. Urol."},{"key":"ref_20","first-page":"6345","article-title":"NMP-22, urinary cytology, and cystoscopy: A 1 year comparison study","volume":"19","author":"Schlake","year":"2012","journal-title":"Can J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4103\/0970-1591.166448","article-title":"Biomarkers for non-muscle invasive bladder cancer: Current tests and future promise","volume":"31","author":"Darwiche","year":"2015","journal-title":"Indian J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.18632\/oncotarget.1744","article-title":"Diagnosis of bladder cancer and prediction of survival by urinary metabolomics","volume":"5","author":"Jin","year":"2014","journal-title":"Oncotarget"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1793\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:06:39Z","timestamp":1760166399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":22,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["diagnostics11101793"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11101793","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,28]]}}}