Current methods for the detection and surveillance of bladder cancer (BCa) are often invasive and/or possess suboptimal sensitivity and specificity, especially in early stage, minimal, residual tumors.
We developed a novel method for the detection of urine tumor DNA Methylation at multiple genomic regions by Mass Array, termed utMeMA. We identified the BCa-specific methylation markers by combined analyses of Sun Yat-sen Memorial Hospital (SYSMH), TCGA and GEO cohorts. The BCa diagnostic model was built in a retrospective cohort (n=313) and validated in a multicenter, prospective cohort (n=175). The performance of this diagnostic assay was analyzed and compared with urine cytology and FISH.
We first discovered 26 significant methylation markers of BCa in combined analyses. We build and validate a two-marker-based diagnostic model that discriminated patients with BCa with high accuracy (86.7%), sensitivity (90.0%) and specificity (83.1%). Furthermore, utMeMA based assay achieved a great improvement in sensitivity over urine cytology and FISH, especially in the detection of early stage (Ta and low grade tumor, 64.5% vs. 11.8%, 15.8%), minimal (81.0% vs. 14.8%, 37.9%), residual (93.3% vs. 27.3%, 64.3%) and recurrent (89.5% vs. 31.4%, 52.8%) tumors. The urine diagnostic score (UD-score) from this assay was better associated with tumor malignancy and burden.
Urine tumor DNA methylation assessment for early diagnosis, minimal, residual tumor detection and surveillance in bladder cancer is a rapid, high-throughput, non-invasive and promising approach, which may reduce the burden of cystoscopy and blind second surgery.
The Journal of clinical investigation. 2020 Aug 20 [Epub ahead of print]
Xu Chen, Jingtong Zhang, Weimei Ruan, Ming Huang, Chanjuan Wang, Hong Wang, Zeyu Jiang, Shaogang Wang, Zheng Liu, Chunxiao Liu, Wanlong Tan, Jin Yang, Jiaxin Chen, Zhiwei Chen, Xia Li, Xiaoyu Zhang, Peng Xu, Lin Chen, Ruihui Xie, Qianghua Zhou, Shizhong Xu, Darryl Irwin, Jian-Bing Fan, Jian Huang, Tianxin Lin
Department of Urology, Sun Yat-Sen University, Guangzhou, China., AnchorDx Medical Co., Ltd., AnchorDx Medical Co., Ltd., Guangzhou, China., Department of Pathology, Southern Medical University, Guangzhou, China., Department of Urology, Huazhong University of Science and Technology, Wuhan, China., Department of Urology, Southern Medical University, Guangzhou, China., Department of Urology, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, China., 1.Department of Urology,2.Guangdong Provincial Key Laboratory of Malignant, Sun Yat-Sen University, Guangzhou, China., Agena bioscience, Inc., Agena bioscience, Inc., San Diego, United States of America.