Abstract
Renal cancer (RC) is the most lethal urological malignancy with 30% late diagnosis. Over 50% RCs are asymptomatic and discovered incidentally. Current RC detection relies on imaging while it lacks satisfactory sensitivity for detecting small-size tumors. A sensitive and robust diagnostic tool is needed to facilitate standardized RC early detection. Herein, we performed genome-wide methylation sequencing on both tissues and urine samples for RC DNA methylation makers discovery and developed a PCR-based RC early detector (RED) using a cohort of 93 RC and 35 non-RC urine samples. RED further achieved sensitivities of 82.2% and 80.7%, and specificities of 77.1% and 75% in a testing cohort (90 RC vs. 35 non-RC) and a validation cohort (119 RC vs. 48 non-RC), respectively. Importantly, RED exhibited 89.5% sensitivity for tumors in diameter <2 cm. It can detect 83.6% clear cell renal cell carcinoma, 75.0% of translocational renal cell carcinoma, 100% of primitive neuroectodermal tumors, renal malignant masenchymomas and mucinous tubular and spindle cell carcinoma. RED showed promising performance for RC detection with early stage and small size and have potential to be used in conjunction with imaging.
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Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (Grant No. 82273412); Special Funding of Department of Finance of Guangdong Province (Grant No. KS0120220267, KS0120220268, KS0120220269, KS0120220270, KS0120220271, KS0120220272); Guangzhou Basic and Applied Basic Research Foundation (Grant No. 202201011030); Scheme of Guangzhou Economic and Technological Development District for Leading Talents in Innovation and Entrepreneurship (Grant No. 2017-L152); Scheme of Guangzhou for Leading Talents in Innovation and Entrepreneurship (Grant No. 2016007); Scheme of Guangzhou for Leading Team in Innovation (Grant No.201909010010); Guangzhou Development Zone International Science and Technology Cooperation Project (Grant No. 2020GH15, 2021GH17); Science and Technology Planning Project of Guangzhou (Grant No. 202206080013).
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X Zhang, Q Huang, J Liu, D Ding and J Fan conceived, designed and directed the study. W Ruan, H Wang, Z Liang developed the methodology. T Shi, H Chen, Z Wang, C Peng, S Huang collected patient samples and acquired the patient information. H Wang, J Zhong perform data analysis and interpretation of data. W Ruan, Z Liang, X Liang, and J Chen performed sample testing and provided technical or material support. T Shi and W Ruan wrote the manuscript. X Pu, L Wang, W Wei and T Li coordinated in patient recruitments. Y Wen and Z Chen reviewed the manuscript. All authors read and approved the final manuscript. The co-first authors T Shi, H Chen, Z Wang, H Wang, C Peng, S Huang and Y Wen contributed equally to this work.
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HW, YW, ZL, JZ, XL, JC, ZC, WR and J-BF are/were employees of AnchorDx Medical Co, Ltd. or AnchorDx, Inc. All other authors declare no competing financial interest.
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The study was performed in compliance with ethical principles of the Declaration of Helsinki. The study was conducted under the approval of the Ethics Committees of the Chinese PLA General Hospital, Guangdong Provincial People’s Hospital and Henan Provincial People’s Hospital. The written informed consent was obtained from all patients.
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Shi, T., Chen, H., Wang, Z. et al. A urine DNA methylation assay for early detection of renal cancer. Oncogene 44, 1709–1717 (2025). https://doi.org/10.1038/s41388-024-03268-x
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DOI: https://doi.org/10.1038/s41388-024-03268-x
