Population-specific molecular features and clinical significance of urinary tumor DNA mutations in Chinese patients with newly diagnosed non-muscle-invasive bladder cancer.
5 affiliations
- 1Department of Urology, Guangyuan Central Hospital of Sichuan Province, Guangyuan, China.
- 2Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
- 3Department of Nursing, Fudan University Shanghai Cancer Center, Shanghai, China.
- 4Shanghai Medical College, Fudan University, Shanghai, China.
- 5Acornmed Biotechnology Co., Ltd, Beijing, China.
Abstract
Background
Non-muscle-invasive bladder cancer (NMIBC) is characterized by high recurrence rates, highlighting the need for effective, non-invasive diagnostic and risk stratification tools. Although urinary biomarkers are increasingly used worldwide, molecular data specific to Chinese NMIBC populations remain limited. This study explores the potential utility of TERT promoter and FGFR3 hotspot mutations detected in urinary tumor DNA (utDNA) in a prospective Chinese cohort.Methods
We prospectively enrolled 106 newly diagnosed NMIBC patients between February 2023 and August 2023 at Fudan University Shanghai Cancer Center (ChiCTR2300076543). First-morning urine samples were collected prior to TURBT. A PCR-based UI-Seek assay was employed to detect hotspot mutations in the promoter region (M1: c.-146 C>T, C250T; M2: c.-124 C>T, C228T) and FGFR3 gene (M1: c.742 C>T, p.R248C; M2: c.746 C>G, p.S249C).Results
The overall mutation rates for TERT promoter and FGFR3 were 49.06% and 15.09%, respectively, with a combined sensitivity of 55.66%. Compared with published study cohorts from Western countries and Japan, Chinese NMIBC patients showed differences in molecular mutation profiles. Notably, the TERT-M2 mutation was associated with tumor aggressiveness, with significant correlations observed for T1 stage (P = 0.011), high-grade tumors (P = 0.011), and high/very high EAU risk categories (P < 0.001). In the subgroup of patients with rapid recurrence within 12 months, TERT promoter mutations (particularly M2), high-grade histology, T1 stage, and high/very high EAU risk categories were significantly enriched. Conversely, FGFR3 mutations showed no significant correlation with clinicopathological parameters. Patients were stratified into early recurrence (≤12 months, n = 14) and long-term recurrence-free (>24 months, n = 40) groups. T1 stage, high tumor grade, high/very high-risk stratification, and TERT mutations (especially the TERT-M2 subtype) were significantly associated with early recurrence (P < 0.05), whereas sex, tumor multiplicity, presence of CIS, and FGFR3 mutations showed no significant correlation with recurrence timing (P > 0.05).Conclusion
This study characterizes the mutational landscape of urinary tumor DNA (utDNA) in Chinese patients with non-muscle invasive bladder cancer (NMIBC). Our findings suggest that utDNA-based detection of TERT promoter mutations, particularly the M2 subtype, and FGFR3 mutations may provide complementary molecular information for recurrence risk assessment. Larger prospective multicenter studies are warranted to validate these findings and evaluate the clinical potential of utDNA as a non-invasive molecular tool in NMIBC management.
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BibTeX
@article{sun2026populationspecific,
title = {{Population-specific molecular features and clinical significance of urinary tumor DNA mutations in Chinese patients with newly diagnosed non-muscle-invasive bladder cancer.}},
author = {Zugang Sun and Run Xie and Jian Pan and Yiping Zhu and Yijun Shen and Chengyuan Gu and Chunguang Ma and Shengming Jin and Huina Wang and Dingwei Ye and Yao Zhu and Junlong Wu},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1914617},
url = {https://europepmc.org/article/MED/42908741},
note = {CC BY},
}
RIS
TY - JOUR
TI - Population-specific molecular features and clinical significance of urinary tumor DNA mutations in Chinese patients with newly diagnosed non-muscle-invasive bladder cancer.
AU - Zugang Sun
AU - Run Xie
AU - Jian Pan
AU - Yiping Zhu
AU - Yijun Shen
AU - Chengyuan Gu
AU - Chunguang Ma
AU - Shengming Jin
AU - Huina Wang
AU - Dingwei Ye
AU - Yao Zhu
AU - Junlong Wu
PY - 2026
DA - 2026/10/07
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1914617
UR - https://europepmc.org/article/MED/42908741
AB - Background Non-muscle-invasive bladder cancer (NMIBC) is characterized by high recurrence rates, highlighting the need for effective, non-invasive diagnostic and risk stratification tools. Although urinary biomarkers are increasingly used worldwide, molecular data specific to Chinese NMIBC populations remain limited. This study explores the potential utility of TERT promoter and FGFR3 hotspot mutations detected in urinary tumor DNA (utDNA) in a prospective Chinese cohort.Methods We prospectively enrolled 106 newly diagnosed NMIBC patients between February 2023 and August 2023 at Fudan University Shanghai Cancer Center (ChiCTR2300076543). First-morning urine samples were collected prior to TURBT. A PCR-based UI-Seek assay was employed to detect hotspot mutations in the promoter region (M1: c.-146 C>T, C250T; M2: c.-124 C>T, C228T) and FGFR3 gene (M1: c.742 C>T, p.R248C; M2: c.746 C>G, p.S249C).Results The overall mutation rates for TERT promoter and FGFR3 were 49.06% and 15.09%, respectively, with a combined sensitivity of 55.66%. Compared with published study cohorts from Western countries and Japan, Chinese NMIBC patients showed differences in molecular mutation profiles. Notably, the TERT-M2 mutation was associated with tumor aggressiveness, with significant correlations observed for T1 stage (P = 0.011), high-grade tumors (P = 0.011), and high/very high EAU risk categories (P < 0.001). In the subgroup of patients with rapid recurrence within 12 months, TERT promoter mutations (particularly M2), high-grade histology, T1 stage, and high/very high EAU risk categories were significantly enriched. Conversely, FGFR3 mutations showed no significant correlation with clinicopathological parameters. Patients were stratified into early recurrence (≤12 months, n = 14) and long-term recurrence-free (>24 months, n = 40) groups. T1 stage, high tumor grade, high/very high-risk stratification, and TERT mutations (especially the TERT-M2 subtype) were significantly associated with early recurrence (P < 0.05), whereas sex, tumor multiplicity, presence of CIS, and FGFR3 mutations showed no significant correlation with recurrence timing (P > 0.05).Conclusion This study characterizes the mutational landscape of urinary tumor DNA (utDNA) in Chinese patients with non-muscle invasive bladder cancer (NMIBC). Our findings suggest that utDNA-based detection of TERT promoter mutations, particularly the M2 subtype, and FGFR3 mutations may provide complementary molecular information for recurrence risk assessment. Larger prospective multicenter studies are warranted to validate these findings and evaluate the clinical potential of utDNA as a non-invasive molecular tool in NMIBC management.
SN - 2234-943X
ER -