A urine DNA methylation assay for early detection of renal cancer

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.