Bisulfite‐free PCDHGB7 methylation in urine enables early noninvasive detection of urothelial carcinoma

Abstract Urothelial carcinomas (UCs) are the fourth most common male malignancies. However, currently implemented detection methods for UC are usually invasive and/or show passable sensitivity and specificity. An accurate, practical, and effective approach is urgently needed for UC clinical detectio...

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Main Authors: Zhicong Yang, Qing Chen, Shihua Dong, Peng Xu, Zhanrui Mao, Yaping Dong, Wei Li, Wenxuan Li, Yang Han, Lihe Dai, Gehong Dong, Yong Zhang, Yinshan Li, Liang Cheng, Weimin Ci, Wenqiang Yu, Chuanliang Xu
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Bioengineering & Translational Medicine
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Online Access:https://doi.org/10.1002/btm2.70004
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author Zhicong Yang
Qing Chen
Shihua Dong
Peng Xu
Zhanrui Mao
Yaping Dong
Wei Li
Wenxuan Li
Yang Han
Lihe Dai
Gehong Dong
Yong Zhang
Yinshan Li
Liang Cheng
Weimin Ci
Wenqiang Yu
Chuanliang Xu
author_facet Zhicong Yang
Qing Chen
Shihua Dong
Peng Xu
Zhanrui Mao
Yaping Dong
Wei Li
Wenxuan Li
Yang Han
Lihe Dai
Gehong Dong
Yong Zhang
Yinshan Li
Liang Cheng
Weimin Ci
Wenqiang Yu
Chuanliang Xu
author_sort Zhicong Yang
collection DOAJ
description Abstract Urothelial carcinomas (UCs) are the fourth most common male malignancies. However, currently implemented detection methods for UC are usually invasive and/or show passable sensitivity and specificity. An accurate, practical, and effective approach is urgently needed for UC clinical detection. Based on the observation that PCDHGB7 was hypermethylated in UC, we developed a bisulfite‐free quantitative polymerase chain reaction (qPCR)‐based PCDHGB7 evaluation to enable urine for UC noninvasive detection. A total of 887 urine samples from UC/benign diseases of the urinary system (BUD) patients between 2022 and 2023 were included. All collected samples were divided into training and validation sets in a 2:1 ratio based on the order of patient enrollment. Results showed that hypermethylated PCDHGB7 exhibited excellent sensitivity of 87.3% (95% CI: 80.7%–92.3%) and specificity of 91.0% (95% CI: 84.8%–95.3%) in efficiently distinguishing UC from BUD patients in the validation set, which is highly consistent with its performance in the training set. Moreover, PCDHGB7 hypermethylation showed promising potential in identifying sessile UC tumors or cases that might be missed in clinical detection and outperformed standard urine cytology in detecting bladder cancer (82.1% vs. 34.5%), ureter cancer (78.1% vs. 34.4%), and renal pelvis cancer (90.9% vs. 22.7%). Overall, bisulfite‐free qPCR‐based PCDHGB7 evaluation in urine provided a noninvasive, easy‐to‐perform, and effective way for UC early detection.
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spelling doaj-art-0af3b1dc9c4d4146944fa794b2b34a922025-08-20T03:25:40ZengWileyBioengineering & Translational Medicine2380-67612025-07-01104n/an/a10.1002/btm2.70004Bisulfite‐free PCDHGB7 methylation in urine enables early noninvasive detection of urothelial carcinomaZhicong Yang0Qing Chen1Shihua Dong2Peng Xu3Zhanrui Mao4Yaping Dong5Wei Li6Wenxuan Li7Yang Han8Lihe Dai9Gehong Dong10Yong Zhang11Yinshan Li12Liang Cheng13Weimin Ci14Wenqiang Yu15Chuanliang Xu16Shanghai Public Health Clinical Center, Huashan Hospital, Cancer Metastasis Institute, Institutes of Biomedical Sciences Fudan University Shanghai ChinaDepartment of Urology, Changhai Hospital Naval Medical University Shanghai ChinaShanghai Public Health Clinical Center, Huashan Hospital, Cancer Metastasis Institute, Institutes of Biomedical Sciences Fudan University Shanghai ChinaShanghai Public Health Clinical Center, Huashan Hospital, Cancer Metastasis Institute, Institutes of Biomedical Sciences Fudan University Shanghai ChinaShanghai Public Health Clinical Center, Huashan Hospital, Cancer Metastasis Institute, Institutes of Biomedical Sciences Fudan University Shanghai ChinaDepartment of Urology, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of radiotherapy Fudan University Shanghai Cancer Center Shanghai ChinaShanghai Public Health Clinical Center, Huashan Hospital, Cancer Metastasis Institute, Institutes of Biomedical Sciences Fudan University Shanghai ChinaCAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, School of Future Technology, Beijing Institute of Genomics University of Chinese Academy of Sciences Beijing ChinaDepartment of Urology, Changhai Hospital Naval Medical University Shanghai ChinaBeijing Tiantan Hospital Capital Medical University Beijing ChinaBeijing Tiantan Hospital Capital Medical University Beijing ChinaPeople's Hospital of Ningxia Hui Autonomous Region Ningxia Medical University Ningxia ChinaDepartment of Pathology and Laboratory Medicine, Department of Surgery (Urology) BrownUniversity Warren Alpert Medical School and the Legorreta Cancer Center, Brown University Providence Rhode Island USACAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, School of Future Technology, Beijing Institute of Genomics University of Chinese Academy of Sciences Beijing ChinaShanghai Public Health Clinical Center, Huashan Hospital, Cancer Metastasis Institute, Institutes of Biomedical Sciences Fudan University Shanghai ChinaDepartment of Urology, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaAbstract Urothelial carcinomas (UCs) are the fourth most common male malignancies. However, currently implemented detection methods for UC are usually invasive and/or show passable sensitivity and specificity. An accurate, practical, and effective approach is urgently needed for UC clinical detection. Based on the observation that PCDHGB7 was hypermethylated in UC, we developed a bisulfite‐free quantitative polymerase chain reaction (qPCR)‐based PCDHGB7 evaluation to enable urine for UC noninvasive detection. A total of 887 urine samples from UC/benign diseases of the urinary system (BUD) patients between 2022 and 2023 were included. All collected samples were divided into training and validation sets in a 2:1 ratio based on the order of patient enrollment. Results showed that hypermethylated PCDHGB7 exhibited excellent sensitivity of 87.3% (95% CI: 80.7%–92.3%) and specificity of 91.0% (95% CI: 84.8%–95.3%) in efficiently distinguishing UC from BUD patients in the validation set, which is highly consistent with its performance in the training set. Moreover, PCDHGB7 hypermethylation showed promising potential in identifying sessile UC tumors or cases that might be missed in clinical detection and outperformed standard urine cytology in detecting bladder cancer (82.1% vs. 34.5%), ureter cancer (78.1% vs. 34.4%), and renal pelvis cancer (90.9% vs. 22.7%). Overall, bisulfite‐free qPCR‐based PCDHGB7 evaluation in urine provided a noninvasive, easy‐to‐perform, and effective way for UC early detection.https://doi.org/10.1002/btm2.70004early noninvasive detectionPCDHGB7 evaluationurothelial carcinoma
spellingShingle Zhicong Yang
Qing Chen
Shihua Dong
Peng Xu
Zhanrui Mao
Yaping Dong
Wei Li
Wenxuan Li
Yang Han
Lihe Dai
Gehong Dong
Yong Zhang
Yinshan Li
Liang Cheng
Weimin Ci
Wenqiang Yu
Chuanliang Xu
Bisulfite‐free PCDHGB7 methylation in urine enables early noninvasive detection of urothelial carcinoma
Bioengineering & Translational Medicine
early noninvasive detection
PCDHGB7 evaluation
urothelial carcinoma
title Bisulfite‐free PCDHGB7 methylation in urine enables early noninvasive detection of urothelial carcinoma
title_full Bisulfite‐free PCDHGB7 methylation in urine enables early noninvasive detection of urothelial carcinoma
title_fullStr Bisulfite‐free PCDHGB7 methylation in urine enables early noninvasive detection of urothelial carcinoma
title_full_unstemmed Bisulfite‐free PCDHGB7 methylation in urine enables early noninvasive detection of urothelial carcinoma
title_short Bisulfite‐free PCDHGB7 methylation in urine enables early noninvasive detection of urothelial carcinoma
title_sort bisulfite free pcdhgb7 methylation in urine enables early noninvasive detection of urothelial carcinoma
topic early noninvasive detection
PCDHGB7 evaluation
urothelial carcinoma
url https://doi.org/10.1002/btm2.70004
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