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TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region

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 identifie...

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Autores principales: Pakmanesh, Hamid, Anvari, Omid, Forey, Nathalie, Weiderpass, Elisabete, Malekpourafshar, Reza, Iranpour, Maryam, Shahesmaeili, Armita, Ahmadi, Nahid, Bazrafshan, Azam, Zendehdel, Kazem, Kannengiesser, Caroline, Ba, Ibrahima, McKay, James, Zvereva, Maria, Hosen, Md Ismail, Sheikh, Mahdi, Calvez-Kelm, Florence Le
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696845/
https://www.ncbi.nlm.nih.gov/pubmed/36430798
http://dx.doi.org/10.3390/ijms232214319
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author Pakmanesh, Hamid
Anvari, Omid
Forey, Nathalie
Weiderpass, Elisabete
Malekpourafshar, Reza
Iranpour, Maryam
Shahesmaeili, Armita
Ahmadi, Nahid
Bazrafshan, Azam
Zendehdel, Kazem
Kannengiesser, Caroline
Ba, Ibrahima
McKay, James
Zvereva, Maria
Hosen, Md Ismail
Sheikh, Mahdi
Calvez-Kelm, Florence Le
author_facet Pakmanesh, Hamid
Anvari, Omid
Forey, Nathalie
Weiderpass, Elisabete
Malekpourafshar, Reza
Iranpour, Maryam
Shahesmaeili, Armita
Ahmadi, Nahid
Bazrafshan, Azam
Zendehdel, Kazem
Kannengiesser, Caroline
Ba, Ibrahima
McKay, James
Zvereva, Maria
Hosen, Md Ismail
Sheikh, Mahdi
Calvez-Kelm, Florence Le
author_sort Pakmanesh, Hamid
collection PubMed
description 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.
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spelling pubmed-96968452022-11-26 TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region Pakmanesh, Hamid Anvari, Omid Forey, Nathalie Weiderpass, Elisabete Malekpourafshar, Reza Iranpour, Maryam Shahesmaeili, Armita Ahmadi, Nahid Bazrafshan, Azam Zendehdel, Kazem Kannengiesser, Caroline Ba, Ibrahima McKay, James Zvereva, Maria Hosen, Md Ismail Sheikh, Mahdi Calvez-Kelm, Florence Le Int J Mol Sci Article 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. MDPI 2022-11-18 /pmc/articles/PMC9696845/ /pubmed/36430798 http://dx.doi.org/10.3390/ijms232214319 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pakmanesh, Hamid
Anvari, Omid
Forey, Nathalie
Weiderpass, Elisabete
Malekpourafshar, Reza
Iranpour, Maryam
Shahesmaeili, Armita
Ahmadi, Nahid
Bazrafshan, Azam
Zendehdel, Kazem
Kannengiesser, Caroline
Ba, Ibrahima
McKay, James
Zvereva, Maria
Hosen, Md Ismail
Sheikh, Mahdi
Calvez-Kelm, Florence Le
TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region
title TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region
title_full TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region
title_fullStr TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region
title_full_unstemmed TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region
title_short TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region
title_sort tert promoter mutations as simple and non-invasive urinary biomarkers for the detection of urothelial bladder cancer in a high-risk region
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696845/
https://www.ncbi.nlm.nih.gov/pubmed/36430798
http://dx.doi.org/10.3390/ijms232214319
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