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A network pharmacology-guided multi-omics and spatial single-cell framework nominates WT1 as a spironolactone-linked immune biomarker in prostate cancer - PubMed

4 hours ago
  • #spironolactone
  • #prostate cancer
  • #WT1
  • Spironolactone (SPI) is a candidate for drug repurposing in prostate cancer (PCa) due to its anti-androgenic activity.
  • The study uses network pharmacology, multi-omics, and spatial single-cell analysis to identify WT1 as a key biomarker linked to SPI in PCa.
  • WT1 is downregulated in PCa tumors but high expression correlates with improved disease-free survival and an 'immune-hot' phenotype.
  • scRNA-seq and spatial transcriptomics show WT1 is heterogeneously expressed in tumor and stromal compartments, particularly in immune-interacting niches.
  • Molecular docking suggests potential SPI-WT1 interaction, and in vitro assays show WT1 restoration suppresses PCa cell proliferation and migration while inducing apoptosis.
  • The study proposes the SPI-WT1 axis as a novel therapeutic target, positioning SPI as a potential immunomodulator in PCa treatment.