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Identification of druggable genetic targets for prostate cancer risk based on mendelian randomization and single-cell

Liantai Song1, Xinyang He1, Yibing Duan1

  • 1Chengde Medical University, Chengde, 067000, China.

International Urology and Nephrology
|April 30, 2025
PubMed
Abstract

Insights

This study identified five key genes (BAK1, ATP1B2, PEMT, TPM3, ZDHHC7) linked to prostate cancer risk, offering potential new targets for precision medicine and drug development.

Area of Science:

  • Genetics and Genomics
  • Oncology
  • Pharmacogenomics

Background:

  • Prostate cancer remains a leading cause of cancer death globally.
  • Identifying novel genetic targets is crucial for developing effective therapies.
  • Advanced genetic analysis offers new avenues for understanding cancer risk and treatment.

Purpose of the Study:

  • To identify druggable genes associated with prostate cancer risk using a multi-omics approach.
  • To validate potential therapeutic targets and diagnostic markers for prostate cancer.
  • To explore the expression patterns and potential side effects of identified genetic targets.

Main Methods:

  • Utilized Mendelian Randomization (MR) and colocalization analysis with prostate cancer Genome-Wide Association Study (GWAS) data.
  • Integrated expression Quantitative Trait Loci (eQTLs) with druggable genome databases to select candidate genes.
  • Employed single-cell RNA sequencing to analyze gene expression in tumor cells and Phenome-Wide Association Studies (PheWAS) for side effect evaluation.

Main Results:

  • Identified 58 genes causally associated with prostate cancer risk via MR, with 12 validated by colocalization.
  • Five genes (BAK1, ATP1B2, PEMT, TPM3, ZDHHC7) showed strong colocalization, indicating high potential as drug targets.
  • Single-cell RNA sequencing revealed enrichment of these genes in prostate tumor T cells and macrophages; PheWAS indicated minimal side effects, except for BAK1.

Conclusions:

  • This study successfully identified and validated novel genetic targets for prostate cancer.
  • The integration of MR, colocalization, and single-cell RNA sequencing enhances target validation accuracy.
  • Findings provide a strong foundation for developing targeted therapies and diagnostic strategies for prostate cancer.
Keywords:
ColocalizationDruggable genomeMendelian randomizationPhenome-wide association studiesProstate cancer

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