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Updated: Mar 18, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
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Methylation and Expression Analysis of POU4F2, HOXA9, RBM46, and TSGA10 Genes in Bladder Cancer Using

Shadi Mahdipour1, Mohammad Hossein Modarressi2, Mehrdad Noruzinia1

  • 1Department of Medical Genetics, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran.

Cancer Management and Research
|March 16, 2026
PubMed
Summary

This study reveals that specific gene methylation and expression changes in urine cell-free DNA (cfDNA) can serve as accurate, non-invasive biomarkers for early bladder cancer detection, outperforming traditional methods.

Keywords:
DNA methylationPCR-based methodsbladder cancercell-free DNAnon-invasive biomarkers

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Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Biomarker Discovery

Background:

  • Bladder cancer diagnosis relies on invasive methods like cystoscopy, with limitations in sensitivity for low-grade tumors.
  • Non-invasive diagnostic advancements focus on cell-free DNA (cfDNA) and DNA methylation for early detection.

Purpose of the Study:

  • To investigate promoter methylation and gene expression alterations of POU4F2, HOXA9, RBM46, and TSGA10 in bladder cancer patients.
  • To evaluate the potential of these genetic changes as non-invasive biomarkers for bladder cancer diagnosis.

Main Methods:

  • Collected urine and plasma samples from 22 bladder cancer patients and 30 controls.
  • Extracted cfDNA and total RNA, assessed methylation via MSRE-PCR, and gene expression via Real-Time PCR.
  • Utilized statistical analysis including unpaired t-test and ANOVA, with ROC analysis for diagnostic performance.

Main Results:

  • Urine cfDNA showed significantly increased promoter methylation for POU4F2, HOXA9, RBM46, and TSGA10 in patients versus controls (p < 0.0001).
  • ROC analysis demonstrated high diagnostic accuracy for individual genes (AUCs 0.88-0.98) and a composite methylation score (AUC 0.993).
  • Gene expression analysis revealed significant downregulation of POU4F2 and HOXA9, and upregulation of RBM46 and TSGA10 in patient urine.

Conclusions:

  • Promoter methylation and expression profiles of the studied genes in urine cfDNA are promising non-invasive biomarkers for early bladder cancer detection.
  • These novel biomarkers offer improved sensitivity and accuracy compared to traditional diagnostic approaches.
  • The findings support the development of more effective non-invasive screening tests for bladder cancer.