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Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets and DNA Methylation-Mediated Regulation

Taoen Li1, Qiang Wei1,2

  • 1Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.

Technology in Cancer Research & Treatment
|May 7, 2026
PubMed

Insights

This study identifies 11 new therapeutic targets for urological cancers, including prostate, renal, and bladder cancers, by integrating multi-omics data. It also reveals DNA methylation

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Urological cancers (prostate, renal, bladder) pose significant health challenges, especially in advanced stages.
  • Limited targeted therapies, drug resistance, and poor prognosis necessitate new therapeutic strategies.
  • Identifying novel molecular targets and understanding their mechanisms is crucial for improving patient outcomes.

Purpose of the Study:

  • To systematically identify novel therapeutic targets for urological cancers using integrated multi-omics data.
  • To elucidate the molecular mechanisms underlying these potential therapeutic targets.
  • To explore DNA methylation-mediated regulatory mechanisms for enhanced therapeutic strategies.

Main Methods:

  • Transcriptome-wide Mendelian randomization (TWMR) analysis using druggable genome data.
  • Integration of cis-expression quantitative trait loci (cis-eQTL) and genome-wide association study (GWAS) data.
  • Validation through drug prediction (DSigDB) and molecular docking (AutoDock Vina), alongside DNA methylation quantitative trait loci (mQTL) analysis.

Main Results:

  • Identified 11 high-confidence therapeutic targets across prostate (BNIP2, KAT5, MMP24, SIK2), renal (GRB10, GPR17), and bladder cancers (CELSR1, GPS1, PROC, GSTM1, KLC3).
  • Molecular docking confirmed favorable drug interactions with identified targets.
  • Elucidated DNA methylation-mediated regulation for PROC, CELSR1, and SIK2, highlighting a gene-expression axis.

Conclusions:

  • The study presents 11 novel therapeutic targets for urological cancers.
  • It is the first to demonstrate DNA methylation-mediated regulation for key targets like PROC and SIK2.
  • Proposes a novel therapeutic strategy combining targeted and epigenetic approaches for precision urological oncology.
Keywords:
DNA methylationMendelian randomization (MR)druggable genomemulti-omics analysistherapeutic targetsurological cancers

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