Hypermethylated TAGMe as a universal-cancer-only methylation marker and its application in diagnosis and recurrence monitoring of urothelial carcinoma

Zhicong Yang ¹, Qing Chen ², Shihua Dong ^1,3

¹Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
²Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China.
³Shanghai Epiprobe Biotechnology Co., Ltd, Shanghai, China.
⁴Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
⁵Department of Bioinformatics, Center for Translational Medicine, Naval Medical University, Shanghai, China.
⁶Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China. jianliny@fmmu.edu.cn.
⁷Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. wenqiangyu@fudan.edu.cn.
⁸Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China. chuanliang_xu@126.com.
⁹Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. chuanliang_xu@126.com.

⁰Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital and Cancer Metastasis Institute and Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Journal of Translational Medicine +

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July 3, 2024

View abstract on PubMed

Summary

A novel urine test, TAGMe (TAG of Methylation), shows high accuracy in diagnosing urothelial carcinoma (UC) and detecting recurrence early. This method offers a less invasive alternative to cystoscopy for UC monitoring.

Area Of Science

Urology
Oncology
Molecular Diagnostics

Background

Urothelial carcinoma (UC) is a common urological malignancy with limited diagnostic and monitoring markers.
Current methods for UC diagnosis and recurrence surveillance lack consistent clinical utility.

Purpose Of The Study

To evaluate TAGMe (TAG of Methylation) as a novel urine-based biomarker for urothelial carcinoma (UC) diagnosis and recurrence monitoring.
To establish and validate the TAGMe assessment using restriction enzyme-based bisulfite-free qPCR.

Main Methods

Analyzed methylation levels in tissue samples and developed the TAGMe assessment in a training cohort (n=567) using bisulfite-free qPCR.
Validated TAGMe performance in a separate cohort (n=198) and monitored TAGMe methylation in urine samples from 57 UC patients post-surgery for six months.

Main Results

TAGMe, a novel Universal-Cancer-Only Methylation (UCOM) marker, was found to be hypermethylated in UC.
The TAGMe urine test demonstrated high sensitivity (88.9%) and specificity (90.0%) in distinguishing UC from benign urinary diseases.
TAGMe abnormality predicted recurrence 3-12 months before clinical detection, offering an early intervention window.

Conclusions

TAGMe urine assessment is an effective, easy-to-perform tool for UC diagnosis and recurrence monitoring.
This novel biomarker may reduce the need for invasive cystoscopies in UC patient surveillance.