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Bladder cancer diagnostic and prognostic models from DNA methylation by multi algorithm machine learning.

Junwen Shen1,2, Zhaojun Li1,2, Rongjiang Wang3,4

  • 1The Department of Urology, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China.

NPJ Precision Oncology
|November 26, 2025
PubMed
Summary
This summary is machine-generated.

Researchers identified key DNA methylation sites for early detection and prognosis of urothelial bladder cancer (UBC). A diagnostic model using four sites and a prognostic model using ten sites showed high accuracy, offering clinical applications for UBC management.

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Area of Science:

  • Oncology
  • Epigenetics
  • Bioinformatics

Background:

  • Urothelial bladder cancer (UBC) poses significant diagnostic and prognostic challenges.
  • Identifying reliable biomarkers for early detection and survival prediction is crucial for improving patient outcomes.

Purpose of the Study:

  • To identify core DNA methylation sites associated with UBC.
  • To develop accurate diagnostic and prognostic models for UBC.
  • To elucidate the epigenetic mechanisms underlying UBC development.

Main Methods:

  • Application of six machine learning algorithms to multi-sample datasets (tissue, blood, urine).
  • Development of diagnostic signatures based on DNA methylation sites.
  • Construction of prognostic signatures for survival prediction.
  • In-depth analysis of associations with survival, pathways, immune infiltration, mutations, and treatment responses.
  • Cellular experiments (Q-PCR, WB, Co-IP, ChIP) to validate epigenetic mechanisms.

Main Results:

  • A diagnostic signature of four DNA methylation sites demonstrated high accuracy in detecting UBC in tissue and urine.
  • A prognostic signature of ten DNA methylation sites effectively predicted patient survival outcomes.
  • Eleven key methylation sites were identified with significant clinical applicability for UBC diagnosis and prognosis.
  • An epigenetic mechanism involving TET2-mediated demethylation of C1QTNFNF6 was identified as a driver of UBC progression.

Conclusions:

  • The study presents novel DNA methylation biomarkers for early diagnosis and prognosis of urothelial bladder cancer.
  • The findings offer a deeper understanding of the epigenetic regulation in UBC, highlighting the roles of TET2 and C1QTNFNF6.
  • These discoveries hold potential for improved clinical management and therapeutic strategies for UBC patients.