{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:46:22Z","timestamp":1769690782877,"version":"3.49.0"},"reference-count":22,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Purpose: To assess the diagnostic performance of urine telomerase activity (TA) in detecting bladder cancer (BCa) using the modified Telomeric Repeat Amplification Protocol (TRAP) and the Real Time Telomeric Repeat Amplification Protocol with double Polymerase Chain Reaction (RT-TRAP-2PCR). Methods: In this case-control study, matching urine (in the pre- and post-surgical period) and tissue samples from 68 patients with BCa were assessed for TA. As a control, 45 urine samples were examined from non-BCa patients. TA levels were measured using TRAP and RT-TRAP-2 PCR methods. Results: Preoperative urinary TA was elevated in 64 (94.1%) of the 68 BCa patients. Urine TA was undetectable in 44 control patients, while TA was detected in one patient with histologically verified cystitis. Sensitivity for BCa detection of 94.1% and specificity of 97.8% were observed for urinary TA, while tissue TA had 100% sensitivity and 97.8% specificity. Both urine and tissue TA levels were not significantly higher in patients with muscle-invasive disease compared to those with non-muscle invasive BCa (p &gt; 0.05). Urine and tissue TA levels were not associated with higher tumor grade, stage, and number of tumors (p &gt; 0.05). However, the association was found between higher urinary and tissue TA levels with tumor size \u2265 3 cm (p = 0.02 and p = 0.01, respectively). During the first postoperative year, 17 BCa patients experienced disease recurrence, and urinary TA was present in 14 (82.4%) of these patients. The sensitivity and specificity of urinary TA levels for BCa recurrence in patients with non-muscle invasive bladder cancer (NMIBC) during follow-up were 82% and 94.4%, respectively. Conclusions: This pilot study demonstrates a high diagnostic performance of urinary and tissue TA levels measured by a new RT-TRAP-2PCR method for detecting and monitoring BCa. Additionally, the association was found between higher urinary and tissue TA levels with tumor size \u2265 3 cm; however, higher TA levels failed for significant correlation with advanced tumor stage and grade. Our study could serve as a benchmark for the evaluation of novel biomarkers using the RT-TRAP-2PCR method.<\/jats:p>","DOI":"10.3390\/jcm10051055","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T21:58:07Z","timestamp":1614895087000},"page":"1055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Detection of Urothelial Bladder Cancer Based on Urine and Tissue Telomerase Activity Measured by Novel RT-TRAP-2PCR Method"],"prefix":"10.3390","volume":"10","author":[{"given":"Alexander","family":"Glukhov","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Sechenov University, 119146 Moscow, Russia"},{"name":"Faculty of Biology, Moscow State University, 119192 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya","family":"Potoldykova","sequence":"additional","affiliation":[{"name":"Institute for Urology and Reproductive Health, Sechenov University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Taratkin","sequence":"additional","affiliation":[{"name":"Institute for Urology and Reproductive Health, Sechenov University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Gordeev","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Moscow State University, 119192 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin","family":"Polyakovsky","sequence":"additional","affiliation":[{"name":"Institute for Urology and Reproductive Health, Sechenov University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8953-0272","authenticated-orcid":false,"given":"Ekaterina","family":"Laukhtina","sequence":"additional","affiliation":[{"name":"Institute for Urology and Reproductive Health, Sechenov University, 119435 Moscow, Russia"},{"name":"Department of Urology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Moschini","sequence":"additional","affiliation":[{"name":"Department of Urology, Luzerner Kantonsspital, 6000 Lucerne, Switzerland"},{"name":"Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele University, 20132 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6603-6319","authenticated-orcid":false,"given":"Mohammad","family":"Abufaraj","sequence":"additional","affiliation":[{"name":"Department of Urology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, The University of Jordan, 11942 Amman, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahrokh F.","family":"Shariat","sequence":"additional","affiliation":[{"name":"Institute for Urology and Reproductive Health, Sechenov University, 119435 Moscow, Russia"},{"name":"Department of Urology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, The University of Jordan, 11942 Amman, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Sekacheva","sequence":"additional","affiliation":[{"name":"Computational Oncology Group, Sechenov University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Enikeev","sequence":"additional","affiliation":[{"name":"Institute for Urology and Reproductive Health, Sechenov University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Glybochko","sequence":"additional","affiliation":[{"name":"Institute for Urology and Reproductive Health, Sechenov University, 119435 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/S0090-4295(03)00236-X","article-title":"Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder","volume":"61","author":"Shariat","year":"2003","journal-title":"Urology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1007\/s00345-018-2380-x","article-title":"An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer","volume":"36","author":"Soria","year":"2018","journal-title":"World J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"574","DOI":"10.4103\/ijdr.IJDR_690_16","article-title":"Telomerase: An exploration toward the end of cancer","volume":"28","author":"Popli","year":"2017","journal-title":"Indian J. Dent. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1002\/pros.22823","article-title":"Telomerase as a tumor marker in diagnosis of prostatic intraepithelial neoplasia and prostate cancer","volume":"74","author":"Glybochko","year":"2014","journal-title":"Prostate"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1126\/science.1218370","article-title":"Wnt\/beta-catenin signaling regulates telomerase in stem cells and cancer cells","volume":"336","author":"Hoffmeyer","year":"2012","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100","DOI":"10.18565\/urology.2018.5.100-105","article-title":"Current trends in bladder cancer diagnosis","volume":"5","author":"Glukhov","year":"2018","journal-title":"Urologiia"},{"key":"ref_7","first-page":"76","article-title":"The role of telomerase activity in non-invasive diagnostics of bladder cancer","volume":"4","author":"Glybochko","year":"2016","journal-title":"Urologiia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/00019606-200209000-00009","article-title":"Realtime quantitative analysis of telomerase activity in breast tumor specimens using a highly specific and sensitive fluorescentbased assay","volume":"11","author":"Elmore","year":"2002","journal-title":"Diagn. Mol. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/clinchem\/47.3.519","article-title":"Real-Time Quantitative Telomeric Repeat Amplification Protocol Assay for the Detection of Telomerase Activity","volume":"47","author":"Hou","year":"2001","journal-title":"Clin. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1373\/clinchem.2004.044727","article-title":"Preparation and Characterization of Candidate Reference Materials for Telomerase Assays","volume":"51","author":"Jakupciak","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1126\/science.7605428","article-title":"Specific association of human telomerase activity with immortal cells and cancer","volume":"266","author":"Kim","year":"1994","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.eururo.2019.08.016","article-title":"European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)\u20132020 Update","volume":"76","author":"Babjuk","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104726","DOI":"10.1016\/j.phrs.2020.104726","article-title":"Telomerase: Key regulator of inflammation and cancer","volume":"155","author":"Wu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3233\/BLC-160065","article-title":"The New Immortalized Uroepithelial Cell Line HBLAK Contains Defined Genetic Aberrations Typical of Early Stage Urothelial Tumors","volume":"2","author":"Hoffmann","year":"2016","journal-title":"Bladder Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nrurol.2017.104","article-title":"Telomeres and telomerase in prostate cancer development and therapy","volume":"14","author":"Graham","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1006\/bbrc.1998.8801","article-title":"Inhibition of telomerase activity of melanoma cells in vitro by antisense oligonucleotides","volume":"248","author":"Glukhov","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13073-016-0324-x","article-title":"Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies","volume":"8","author":"Jafri","year":"2016","journal-title":"Genome Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1177\/172460080902400406","article-title":"Accuracy of urine telomerase activity to detect bladder cancer in symptomatic patients","volume":"24","author":"Casadio","year":"2009","journal-title":"Int. J. Biol. Markers"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4103\/0970-1591.45535","article-title":"The current role of telomerase in the diagnosis of bladder cancer","volume":"25","author":"Bravaccini","year":"2009","journal-title":"Indian J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7376","DOI":"10.1158\/0008-5472.CAN-11-1154","article-title":"Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression","volume":"71","author":"Putluri","year":"2011","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/MOU.0000000000000602","article-title":"The interaction of gender and smoking on bladder cancer risks","volume":"29","author":"Janisch","year":"2019","journal-title":"Curr. Opin. Urol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/5\/1055\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:32:36Z","timestamp":1760160756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/5\/1055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,4]]},"references-count":22,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["jcm10051055"],"URL":"https:\/\/doi.org\/10.3390\/jcm10051055","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,4]]}}}