MP16-16: A cost-effective diagnostic approach of urothelial carcinomas in 2 mL urine samples based on a novel panel of dual methylated DNA markers
Friday, May 3, 2024 1:00 PM to 3:00 PM · 2 hr. (US/Central)
221B
Abstract
Information
Full Abstract and Figures
Author Block
Yucai Wu*, Beijing, China, Tingting Li, Wuhan, China, Shiming He, Liqun Zhou, Xuesong Li, Beijing, China
Introduction
This study aimed to identify universal markers for bladder cancer (Bca) and upper urinary tract urothelial carcinoma (UTUC) based on 2 mL of urine samples.
Methods
First, the differentially methylated regions (DMRs) were identified with a sliding window method using the TCGA cohort and validated in 50 normal samples (30 blood cell and 20 urine) by Sanger sequencing. Three novel DMRs with specificity =90% were further validated in 103 tissues including 47 Bca and 28 paired UTUC and NAT (14 renal pelvis and 14 ureter), two reported Bca biomarkers, TWIST1 and VIM, were also detected for comparison using methylation-specific PCR, and four DMRs/biomarkers (Chr10:101140373-101140735 (hg38), AL021918.2[M25], TWIST1 and VIM ) with AUC values higher than 0.7 were further tested in 2 mL of urine from 477 participants (199 Bca, 39 renal pelvis carcinomas, 26 ureter carcinomas, and 213 other urological carcinomas/ benign diseases) by methylation-specific PCR.
Results
The novel biomarker AL021918.2 outperformed the two existing BCa marker both in detecting Bca and UTUC, specifically, its sensitivities for low-grade (LG) Bca, Ta-stage Bca, and LGUTUC were 75.56%, 83.33%, and 100%, respectively, and its overall sensitivity and specificity for urothelial carcinomas were 87.12% and 93.90%, respectively. The combination of AL021918.2 and VIM had an accuracy of >90% for urothelial carcinomas, even for the Ta stage and LG carcinomas, and the overall sensitivity and specificity of the dual-target panel were 93.94%, and 92.02%, respectively.
Conclusions
In this study, we identified a novel and general urothelial carcinoma biomarker AL021918.2 on a genome-wide scale using a sliding window method, and it outperformed the two existing bladder cancer biomarkers TWIST1 and VIM. When AL021918.2 and VIM were combined, the accuracy of the dual-target panel for hardest-to-detect Ta stage and low-grade urothelial carcinomas reached >90%. The non-invasive approach was based on only 2 mL full voided urine, providing a convenient diagnostic tool for urothelial carcinomas.
Source Of Funding
This research is supported by grants from the National Natural Science Foundation of China (No. 82273350, No. 81972380, No. 81872083, and No. 81772703), Beijing Municipal Science & Technology Commission Project (No. Z201100005420029) and National High Level Hospital Clinical Research Funding (Scientific Research Seed Fund of Peking University First Hospital, No.2022SF18).
Author Block
Yucai Wu*, Beijing, China, Tingting Li, Wuhan, China, Shiming He, Liqun Zhou, Xuesong Li, Beijing, China
Introduction
This study aimed to identify universal markers for bladder cancer (Bca) and upper urinary tract urothelial carcinoma (UTUC) based on 2 mL of urine samples.
Methods
First, the differentially methylated regions (DMRs) were identified with a sliding window method using the TCGA cohort and validated in 50 normal samples (30 blood cell and 20 urine) by Sanger sequencing. Three novel DMRs with specificity =90% were further validated in 103 tissues including 47 Bca and 28 paired UTUC and NAT (14 renal pelvis and 14 ureter), two reported Bca biomarkers, TWIST1 and VIM, were also detected for comparison using methylation-specific PCR, and four DMRs/biomarkers (Chr10:101140373-101140735 (hg38), AL021918.2[M25], TWIST1 and VIM ) with AUC values higher than 0.7 were further tested in 2 mL of urine from 477 participants (199 Bca, 39 renal pelvis carcinomas, 26 ureter carcinomas, and 213 other urological carcinomas/ benign diseases) by methylation-specific PCR.
Results
The novel biomarker AL021918.2 outperformed the two existing BCa marker both in detecting Bca and UTUC, specifically, its sensitivities for low-grade (LG) Bca, Ta-stage Bca, and LGUTUC were 75.56%, 83.33%, and 100%, respectively, and its overall sensitivity and specificity for urothelial carcinomas were 87.12% and 93.90%, respectively. The combination of AL021918.2 and VIM had an accuracy of >90% for urothelial carcinomas, even for the Ta stage and LG carcinomas, and the overall sensitivity and specificity of the dual-target panel were 93.94%, and 92.02%, respectively.
Conclusions
In this study, we identified a novel and general urothelial carcinoma biomarker AL021918.2 on a genome-wide scale using a sliding window method, and it outperformed the two existing bladder cancer biomarkers TWIST1 and VIM. When AL021918.2 and VIM were combined, the accuracy of the dual-target panel for hardest-to-detect Ta stage and low-grade urothelial carcinomas reached >90%. The non-invasive approach was based on only 2 mL full voided urine, providing a convenient diagnostic tool for urothelial carcinomas.
Source Of Funding
This research is supported by grants from the National Natural Science Foundation of China (No. 82273350, No. 81972380, No. 81872083, and No. 81772703), Beijing Municipal Science & Technology Commission Project (No. Z201100005420029) and National High Level Hospital Clinical Research Funding (Scientific Research Seed Fund of Peking University First Hospital, No.2022SF18).