{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:14:45Z","timestamp":1787505285572,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kerman University of Medical Sciences"},{"name":"International Agency for Research on Cancer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bladder cancer (BC) is the 10th most common cancer in the world. While there are FDA-approved urinary assays to detect BC, none have demonstrated sufficient sensitivity and specificity to be integrated into clinical practice. Telomerase Reverse Transcriptase (TERT) gene mutations have been identified as the most common BC mutations that could potentially be used as non-invasive urinary biomarkers to detect BC. This study aims to evaluate the validity of these tests to detect BC in the Kerman province of Iran, where BC is the most common cancer in men. Urine samples of 31 patients with primary (n = 11) or recurrent (n = 20) bladder tumor and 50 controls were prospectively collected. Total urinary DNA was screened for the TERT promoter mutations (uTERTpm) by Droplet Digital PCR (ddPCR) assays. The performance characteristics of uTERTpm and the influence by disease stage and grade were compared to urine cytology results. The uTERTpm was 100% sensitive and 88% specific to detect primary BC, while it was 50% sensitive and 88% specific in detecting recurrent BC. The overall sensitivity and specificity of uTERTpm to detect bladder cancer were 67.7% and 88.0%, respectively, which were consistent across different tumor stages and grades. The most frequent uTERTpm mutations among BC cases were C228T (18\/31), C250T (4\/31), and C158A (1\/31) with mutant allelic frequency (MAF) ranging from 0.2% to 63.3%. Urine cytology demonstrated a similar sensitivity (67.7%), but lower specificity (62.0%) than uTERTpm in detecting BC. Combined uTERTpm and urine cytology increased the sensitivity to 83.8%, but decreased the specificity to 52.0%. Our study demonstrated promising diagnostic accuracy for the uTERTpm as a non-invasive urinary biomarker to detect, in particular, primary BC in this population.<\/jats:p>","DOI":"10.3390\/ijms232214319","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T02:52:21Z","timestamp":1668999141000},"page":"14319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5534-7042","authenticated-orcid":false,"given":"Hamid","family":"Pakmanesh","sequence":"first","affiliation":[{"name":"Department of Urology, School of Medicine, Shahid Bahonar Hospital, Kerman University of Medical Sciences, Kerman 7616913555, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7081-5876","authenticated-orcid":false,"given":"Omid","family":"Anvari","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine, Shahid Bahonar Hospital, Kerman University of Medical Sciences, Kerman 7616913555, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Forey","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer (IARC), Genomic Epidemiology Branch, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabete","family":"Weiderpass","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer (IARC), Genomic Epidemiology Branch, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Malekpourafshar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman 7616913555, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Iranpour","sequence":"additional","affiliation":[{"name":"Department of Pathology, Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman 7616913555, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-319X","authenticated-orcid":false,"given":"Armita","family":"Shahesmaeili","sequence":"additional","affiliation":[{"name":"HIV\/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman 7616913555, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahid","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman 7616913555, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azam","family":"Bazrafshan","sequence":"additional","affiliation":[{"name":"HIV\/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman 7616913555, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazem","family":"Zendehdel","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran 1419733133, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2155-9383","authenticated-orcid":false,"given":"Caroline","family":"Kannengiesser","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bichat Claude Bernard Hospital, 75108 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5338-3883","authenticated-orcid":false,"given":"Ibrahima","family":"Ba","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bichat Claude Bernard Hospital, 75108 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"McKay","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer (IARC), Genomic Epidemiology Branch, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7432-1574","authenticated-orcid":false,"given":"Maria","family":"Zvereva","sequence":"additional","affiliation":[{"name":"Chair of Chemistry of Natural Compounds, Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0862-7206","authenticated-orcid":false,"given":"Md Ismail","family":"Hosen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Dhaka, Dhaka 1000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Sheikh","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer (IARC), Genomic Epidemiology Branch, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0063-5068","authenticated-orcid":false,"given":"Florence Le","family":"Calvez-Kelm","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer (IARC), Genomic Epidemiology Branch, 69008 Lyon, 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