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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 <jats:italic>PCDHGB7<\/jats:italic> was hypermethylated in UC, we developed a bisulfite\u2010free quantitative polymerase chain reaction (qPCR)\u2010based <jats:italic>PCDHGB7<\/jats:italic> 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 <jats:italic>PCDHGB7<\/jats:italic> exhibited excellent sensitivity of 87.3% (95% CI: 80.7%\u201392.3%) and specificity of 91.0% (95% CI: 84.8%\u201395.3%) in efficiently distinguishing UC from BUD patients in the validation set, which is highly consistent with its performance in the training set. Moreover, <jats:italic>PCDHGB7<\/jats:italic> 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\u2010free qPCR\u2010based <jats:italic>PCDHGB7<\/jats:italic> evaluation in urine provided a noninvasive, easy\u2010to\u2010perform, and effective way for UC early detection.<\/jats:p>","DOI":"10.1002\/btm2.70004","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T09:16:49Z","timestamp":1741684609000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bisulfite\u2010free <i>PCDHGB7<\/i> methylation in urine enables early noninvasive detection of urothelial carcinoma"],"prefix":"10.1002","volume":"10","author":[{"given":"Zhicong","family":"Yang","sequence":"first","affiliation":[{"name":"Shanghai Public Health Clinical Center, Huashan Hospital, Cancer Metastasis Institute, Institutes of Biomedical Sciences Fudan University  Shanghai 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