A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer

作者：Ruan, Weimei; Chen, Xu; Huang, Ming; Wang, Hong; Chen, Jiaxin; Liang, Zhixin; Zhang, Jingtong; Yu, Yanqi; Chen, Shang; Xu, Shizhong; Hu, Tianliang; Li, Xia; Guo, Yuanjie; Jiang, Zeyu; Chen, Zhiwei^*; Huang, Jian^*; Lin, Tianxin^*; Fan, Jian-Bing^*

来源：Clinical Epigenetics, 2021, 13(1): 91.

DOI：10.1186/s13148-021-01073-x

• Bladder cancer
• DNA methylation assay
• Early detection
• Risk stratification

BackgroundCurrent non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications.MethodsA urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n=192) and Cohort 2 (n=98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n=174) was used as a second validation of the model.ResultsThe assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7-77.8% vs. 0.0-22.2%, 0.0-22.2%), Ta tumor (83.3% vs. 22.2-41.2%, 44.4-52.9%) and non-muscle invasive BC (NMIBC) (80.0-89.7% vs. 51.5-52.0%, 59.4-72.0%) in both cohorts. The assay also had higher accuracies (88.9-95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6-70.8%) and FISH (72.2-77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2.ConclusionsThe urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

• 单位
  南方医科大学; 中山大学